<![CDATA[Revelation of Fire]]>https://www.revfire.ushttps://www.revfire.us/img/substack.pngRevelation of Firehttps://www.revfire.usSubstackMon, 18 May 2026 04:34:01 GMT<![CDATA[El Mecanismo de la Medicina ]]>https://www.revfire.us/p/la-mechanisma-de-la-medicinahttps://www.revfire.us/p/la-mechanisma-de-la-medicinaFri, 07 Jun 2024 03:13:45 GMT

I live in a city and country with lots of humidity and very poor building standards. In this and similar environments, I’ve found myself with a high reactivity to indoor mold. Given my longstanding interest in unorthodox, but legit health solutions, I’ve been working though various options to save my brain from the short term and long term consequences of neuroinflammation. 

Thanks for reading Revelation of Fire! Subscribe for free to receive new posts and support my work.

I’ve had both my physical and cosmic eyes on the metabolic effects of psychedelics for some time now. So I was recently surprised when I found that some psychedelics activate a receptor located on the membrane between endoplasmic reticulum and the mitochondria called the sigma-1 receptor (SIR). While there is a lot of work trying to decipher the full effects and nuance of the receptor, the therapeutic potential seems large.

Here are some paper titles to give a sense of the potential with sigma-1 agonism:

A number of substances activate this receptor and many seem to have positive physical and behavioral effects. Of those N,N-Dimethyltryptamine (DMT) seems to have some of the most clear evidence behind its effects. 

The sigma-1 receptor is expressed in a variety of known tissues: the nervous system, retina, kidney, liver, lung and heart (source). The sigma-1 receptor membrane is critical to energy regulation of the cell.

Sigma-1 activation stabilizes critical components of cells including the mitochondria and mitochondria-associated membrane while improving intracellular calcium status and reducing excitotoxicity. The reduction of excitotoxicity is another way of saying that the cell is more energized. It might seem paradoxical, but more energized cells are relaxed. A fully energized cell is full of potential chemical energy, somewhat like a battery waiting to discharge. “Deficiencies in energy supply are particularly damaging to neurons, which have a high energy demand” (source). Conversely, a well energized cell is relaxed and ready to execute its primary function as required.

Activating the sigma receptor shows promise for a wide range of central nervous system disorders and injuries. Some studies call it neurorestorative and neuroprotective (source) and others have found promise in treating animal models of PTSD (source). The form or vehicle of DMT in the later study was the ayahuasca brew which is often a drink of leaves containing DMT and vine containing a variety of harmala alkaloids that inhibit the breakdown of dopamine and serotonin as well as having their own psychotropic effects. While psychedelics as “drugs” have long been demonized in the west, the consideration of plant medicines as medicine is being revalidated in academia. Based on the studies presented here they are quite broad in their applicability.

“Neuroprotection appears to be due to inhibition of cellular Ca2+ toxicity and/or inflammation, and neurorestoration may include balancing aberrant neurotransmission or stimulation of synaptogenesis, thus remodelling brain connectivity. The Sig-1R is therefore a strong therapeutic target for the development of new treatments for neurodegenerative diseases and stroke.” (source).

All the above said, we cannot expect the existing regulatory framework to evaluate DMT or ayahuasca coherently for a variety of reasons, the lack funding and lack of profit incentives chief among them. Despite that, we can deduce that safety is well established by the pre-existing epochs of human use. In that light, and with the basic physiological research linked to in this essay, it seems the risk-to-benefit ratio runs in complete contradisctinction to the fears conjured by our culture.  

For the times, places, and persons not suitable for psychedelics there are a number of known molecules that activate the sigma-1 receptor while not facilitating a psychedelic experience:

  1. Fluvoxamine

  2. DHEA

  3. Pregnenalone

  4. Estrogen

  5. Berberine

An odd and potentially relevant curiosity is that berberine (typically considered a glucose regulation drug) and DHEA (a steroid/neurosteroid) are both monoamine oxidase inhibitors while not typically being considered as such.

The sigma-1 receptor plays several roles related to energy metabolism at the organism level. It both protects beta cells and promotes their proliferation. Beta cells are pancreatic cells critically related to the regulation of glucose and insulin. The overexpression of sigma-1 receptors in model animals (a proxy for receptor activation), also demonstrates a reduction in insulin secretion under stress (source). This is inline with the fact that sigma-1 receptor activation seems to make all affected cells simply work more efficiently. In turn, that efficiency reduces inflammation and neuroinflammation.

Most relevant to my mold journey is that DMT and 5-MEO-DMT have both been shown to play roles as immune regulatory molecules in both innate and adaptive immune systems:  “Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigma-1 ... Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.” The question remains as to whether other SIR agonists also modulate the immune system.

APPENDIX (further supporting evidence and related curiosities)

DMT:

According to these data, DMT may be considered as adjuvant pharmacological therapy in the management of acute cerebral ischemia.

“DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.”

Ayahuasca:

This study concludes the anxiolytic and antidepressant potential of ayahuasca in an animal model of neuroinflammation, possibly due to the antineuroinflammatory effects already reported of the compound. 

“Patients treated with ayahuasca showed a significant correlation (rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion”

“Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial”

“Ayahuasca's components also seem to modulate levels of inflammatory and neurotrophic factors beneficially. On a biological level, this translates into neuroprotective and neuroplastic effects.”

“ratings of depression and stress significantly decreased after the ayahuasca ceremony and these changes persisted for 4 weeks” 

AutoImmunity:

Potentially by their immunomodulatory activity and in part through the mobilization of cell-intrinsic neuroprotective mechanisms, psychedelics may represent a promising intervention for autoimmune-related depression and other mental illness. 

Active duty military personnel with PTSD may have an elevated risk of a range of autoimmune diseases, regardless of combat experience or prior trauma. 

Neurosteroids & Mental Health:

“In clinical studies, some sigma-1 receptor agonists, including fluvoxamine, donepezil and neurosteroids, improve cognitive impairment and clinical symptoms in neuropsychiatric diseases.”

“Blockade of sigma-1 receptor significantly inhibited the generation of ROS and activation of the MAPK and Akt pathways. These findings underscore the critical role of the sigma-1 receptor in methamphetamine-induced microglial activation.”

The sigma-1 receptor (Sig-1R) is a chaperone receptor that primarily resides at the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) and acts as a dynamic pluripotent modulator regulating cellular pathophysiological processes. Multiple pharmacological studies have confirmed the beneficial effects of Sig-1R activation on cellular calcium homeostasis, excitotoxicity modulation, reactive oxygen species (ROS) clearance, and the structural and functional stability of the ER, mitochondria, and MAM. 

Other SIR-1:

“Sig-1R ligands in preclinical models have significantly beneficial effects associated with improved cardiac function, ventricular remodeling, hypertrophy reduction, and, in the kidney, reduced ischemic damage.”

SIR-1 & Retina

“Sigma1R may be a novel retinal stress modulator, and targeting it even after disease onset may afford retinal neuroprotection.”

Sig‑1R overexpression was found to promote β‑cell proliferation by accelerating cell cycle progression. Furthermore, Sig‑1R overexpression ameliorated the apoptosis rate whilst impairing insulin secretion induced by palmitic acid by relieving ER stress and mitochondrial dysfunction in MIN6 cells. Sig‑1R overexpression also promoted Ca2+ transport between mitochondria and ER by increasing the quantity of ER adjacent to mitochondria in the 50‑nm range. It was concluded that Sig‑1R overexpression conferred protective effects on β‑cells against lipotoxicity as a result of the promotion of cell proliferation and inhibition of ER stress and oxidative stress, by regulating the structure of MAM. 

Psychedelics & Personality:

Neuroticism scores significantly decreased while Extraversion increased following psilocybin therapy. These changes were in the direction of the normative NEO-PI-R data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. Openness scores also significantly increased following psilocybin, whereas Conscientiousness showed trend-level increases, and Agreeableness did not change.

degree of insightfulness during the psychedelic experience predicted changes in Neuroticism and Extraversion. 

“reduced connectivity between the left amygdala and ACC may impair extinction of the amygdala response to anxiety-eliciting stimuli. Second, the neural evidence matches the psychological findings, which associate N with a negative bias in attention, interpretation and recall of information, increased reactivity, and ineffective coping, and is consistent with findings of decreased cardiovascular flexibility. Third, current studies suggest that HPA-axis influences mood independently of N”

“that personality traits were mostly unrelated to resting metabolic rate and energy expenditure at normal walking pace. However, those who scored lower on neuroticism (r =  −0.12) and higher on extraversion (r = 0.11), openness (r = 0.13), and conscientiousness (r = 0.09) had significantly higher energy expenditure at peak walking pace. In addition to greater aerobic capacity, individuals with a more resilient personality profile walked faster and were more efficient in that they required less energy per meter walked. The associations between personality and energy expenditure were not moderated by age or sex, but were in part explained by the proportion of fat mass.” 

In conclusion, the findings suggest that high neuroticism is related to elevated levels of plasma leptin/adiponectin ratio, leptin and IL-6 in young adults. 

Results: Neuroticism correlated positively with frontolimbic serotonin 2A receptor binding [r(79) = .24, p = .028]. Post hoc analysis of the contributions from the six constituent traits of neuroticism showed that the correlation was primarily driven by two of them: vulnerability and anxiety. Indeed, vulnerability, defined as a person's difficulties in coping with stress, displayed the strongest positive correlation, which remained significant after correction for multiple comparisons (r = .35, p = .009). 

Berberine:

“Berberine can be used to treat many diseases, such as cancer and digestive, metabolic, cardiovascular, and neurological diseases. Berberine has protective capacities in digestive diseases. It can inhibit toxins and bacteria, including Helicobacter pylori, protect the intestinal epithelial barrier from injury, and ameliorate liver injury. Berberine also inhibits the proliferation of various types of cancer cells and impedes invasion and metastasis....Berberine also improves cardiovascular hemodynamics, suppresses ischemic arrhythmias, attenuates the development of atherosclerosis, and reduces hypertension. Berberine shows potent neuroprotective effects, including antioxidative, antiapoptotic, and anti-ischemic. Furthermore, berberine exerts protective effects against other diseases.” (source) 

Thanks for reading Revelation of Fire! Subscribe for free to receive new posts and support my work.

]]><![CDATA[Turning into Winter ]]>https://www.revfire.us/p/turning-into-winterhttps://www.revfire.us/p/turning-into-winterSun, 29 Oct 2023 02:23:43 GMTThis is the chart that I tapped out rather carefully. I’ve highlighted the key cell in green.

“Sometime before the year 2025, America will pass through a great gate in history, commensurate with the American Revolution, Civil War, and twin emergencies of the Great Depression and World War II.”

William Strauss & Neil Howe, The Fourth Turning: What the Cycles of History Tell Us About America's Next Rendezvous with Destiny (published 1 Dec 1996)

I strongly expect we’ve arrived at the (kinetic) origins of a big global event. The foresight of the authors above seems to be amazing and uncomfortable. This year Neil published The 4th Turning is Here, a book updating and extending the previous previous collaboration with Bill Strauss. They mapped the many recent cycles of human generations and how the cycles recur and reform. In his model are cycles with four seasons of approximately 20 years each. Each generation comes to adulthood in a sort of season much like the annual seasons. Baby boomers actually faced the springtime of love and millennials the autumn of good vibes.

The fourth season in each cycle is the one that most directly experiences widespread conflict as charted above. The last to experience this was the generation we now call “The Greatest Generation” and the new generation’s crucible seems to have arrived. If the model holds we are now witnessing the inevitable sweep of a persistent force toward tangible kinetic conflict and the horrors that brings.

In rough agreement with Strauss and Howe are at least a few other hyper-intelligent prophetic analysts, who from different angles and mechanisms seem to be describing the same overarching pattern:

Peter Turchin, has a 2023 book aptly titled “End Times”; Ray Dalio, recently published “The Changing World Order”; and George Friedman in 2020 put out “The Storm Before the Calm”.

These are not lightweight efforts, Friedman, Howe’s, and Turchin’s analysis on these cycles started independently around 4 decades ago and have remained independent efforts.

On the one hand, I hope, they are all wrong but the collective analysis seems to me to point to real dynamics, dynamics that in fascinating and terrifying ways seem to transcend all the other major changes that occur through history. 

They are all fairly directly saying: that now is a time of chaos and conflict, and while it has been easier to see it as a guess and a future problem in past reads, it seems reasonable to take their prophecies more seriously as events seem to be unfolding. Maybe, hopefully, we will all be wrong.

However, with that context. I believe global energy production is the place where the heaviest cascading dominoes make contact. Rolling feedforward when energy is taken off the global market accelerates discord. 

If one or more major energy exporters lose the ability to export there is a good chance that global energy supply decreases and prices significantly increase. When that happens the world’s poor become poorer. That increase in impoverishment is like sparklers falling on a parched forest floor. Humans hate a regress in their quality of life and are apt to do the most about it when existing on the knife’s edge of survival.

Despite economists and environmentalists perpetually ignoring the obvious, petrochemical energy prices are the base of all economic prices and the base of all quality of life for most humans. Another way to say the same thing is that the command of calories any individual has in society is his or her wealth.

When energy prices go up, transportation, production, & food prices also go up…relative to your time, your labor & your life. This is not the inflation emphasized by money printing. These prices go up, up in real terms regardless of the way the government handles money. In the short term, there is little governments can do to make it better. Efficiencies help, but more energy is ultimately the answer.

When we as individuals run out of energy we cease to exist. Before that happens; however, we usually become irritable and rebellious and so too our nation-states become bellicose and monger for war.

Leaders get nervous as local conditions deteriorate and the poor become restless. They point their sabers at foreign enemies while internal contenders mount plans to ascend and overthrow.  As history suggests, internal political rivals are often the first enemies to be targeted on the way toward militarism and external conflict.

As of late October 2023, It seems Russian energy supplies were more than replaced by a combination of substitutes and simple redirections to new purchasers. Power and profits have changed hands but so far, the total global energy including natural gas has remarkably been stable and in some cases even increased. The below is natural gas production which includes a 12% drop in Russian exports made up for by the US, Canada, the Middle East, China, Australia, and others. 

Here is the total global energy production which is continues to increase. 

Below is the blurb from the chart from website, EnerData:

Global energy production accelerated in 2022 (+3.7%), much above its 2010-2019 average (+1.6%/year). The growth was driven by China (+5.6%), the United States (+5.8%), Saudi Arabia (+15%), India (+7.9%), Indonesia (+9.4%) and Brazil (+7.8%) and partly offset by a drop in Russia (-4.4%), the European Union (-6.2%) and Africa (-0.9% due to Nigeria and South Africa).

The globe has managed the RU/UKR energy crisis remarkably well. The below graphic shows where excess supply can and has come from. We can see in this chart that the significant current global vulnerability is Iran.  Perhaps Iran knows it has increased relative power and through Hamas is or was gambling or flexing its muscle. Could they have assumed countries of the globe would feel dependent?

We all need cheap energy to maintain internal and external stability.  I wonder if even larger actors are not also playing them and us and easily we are falling for it.

Our political class has an incentive to maintain power and one of the best mechanisms and distractions is a war. As such, there seems to be a US bipartisan momentum for antagonizing Iran and complementary rhetoric from Iran against Israel’s now live incursion into Gaza. Israel has crossed the Rubicon as far as Iran initially warned. Globally countries are being forced to take sides. In recent days, Turkey, a member of the EU with a large standing military, has publicly supported Hamas despite its economic and political ties to the West. Many countries are finding themselves in difficult positions torn between popular sentiment and existing economic or political interests. I hate re-iterating the news, but my main point is that bifurcating sides are being taken and tensions are rising in a global feedforward loop that few understand and likely none can control.

A US conflict with Iran with the proxy war raging in Ukraine might qualify itself as a global war, but I’ve got my attention glued to the second and third-order effects. What would an energy and food price squeeze do to other parts of the world? 

There are almost certainly fissures below the surface in many societies. Ones we cannot predict. Of relevant note, we did not predict the fall of the Berlin Wall and we did not predict the Arab Spring. So as much as I might like to know, I don’t think any of us can really know what other fires start with new increases in prices simultaneous to Religious fervor, credit deflation, and foreign capital retractions from much of the world. 

God speed in and through these “interesting” times.

Afterword: An excerpt from Peter Turchin’s End Times 

“When the equilibrium between ruling elites and the majority tips too far in favor of elites, political instability is all but inevitable. As income inequality surges and prosperity flows disproportionately into the hands of the elites, the common people suffer, and society-wide efforts to become an elite grow ever more frenzied... the wealth pump; it’s a world of the damned and the saved. And since the number of such positions remains relatively fixed, the overproduction of elites inevitably leads to frustrated elite aspirants, who harness popular resentment to turn against the established order.” 

Turchin’s models show that when this state has been reached, societies become locked in a spiral very hard to exit.

“In America, the wealth pump has been operating full blast for two generations. As cliodynamics shows us, our current cycle of elite overproduction and popular immiseration is far along the path to violent political rupture. ”

References:

The Fourth Turning (interview): What past generations can teach us about our future

The Fourth Turning is Here

End Times: Elites, Counter-Elites, and the Path of Political Disintegration

Changing World Order

War, Peace & War

Storm Before the Calm

]]><![CDATA[Moldy]]>https://www.revfire.us/p/moldyhttps://www.revfire.us/p/moldyWed, 20 Sep 2023 05:05:06 GMTI’ve been yearning to write a post for a while, but I’ve been caught in a bit of an energetic tailspin. Outside of my working hours, I’ve been trying to dig out of a metabolic hole from biotoxin exposure. For about a year I’ve been hammered. Luckily, I’ve been learning and finding resources as I sort of flail in the muck. Water-damaged buildings are much more prevalent than one might imagine and with bigger impacts.

Sleeping in moldy spaces (on a pile of antihistamines), I’ve had nightmares, and I’ve been a nightmare. The inflammation from these unseeable substances is expressed initially as irritability and feels a lot like low blood sugar, high anxiety, and high blood pressure. I would not want to be around myself while I’m in mold, though these days when the symptoms are more obvious I have at least a chance of not projecting the bodily feeling onto any unsuspecting other.

Being reactive to a large swath of geography (cities, countries, coasts) begs questions about how to live going forward. It also offers a reconsideration of many events and epochs of my past. As one of many examples in 2010, I left the military and went to Austin, I thought I was allergic to a plant species native to Texas, but in newer light, it seems I initially resided in a water-damaged building. A large percentage of the Airbnbs I’ve been to have not been good. Relatedly, I took a weekend trip about a year ago to reconnect with a now ex. During that weekend I was not easy to be around. We were both probably directly affected. I am sure I was. Sleep-deprived, irritable, two people literally poisoned against one another by the room and its air, but also unaware and projecting their inner states onto the other.

I don’t have allergies when I’m not in a moldy environment. Not dust, not pollen, maybe not even grass to which I was allergic as a kid. Yet, I have had lots of allergies living and working in the last decade. In Washington DC, in New Zealand, and then again back in Maryland all coincident with allergies. Visits to New York occasionally gave me asthma. All these immune responses relate to the quality of the buildings I stayed in. Many buildings have had water damage and most owners are blissfully ignorant or sometimes malevolently complicit in ignoring the problem. I can recall how much better it was to sleep in various places in Raleigh than any of the places near Washington, DC. 

A new house is also no guarantee of reprieve. I went to great lengths to secure a newly built flat, but the carpet and perhaps the paint is now triggering my hyper-vigilant or overtaxed immune system. Toxic molds give off not only spores but also volatile organic compounds (VOCs) and those end up sensitizing or overwhelming the same system that would detoxify similar compounds from newly installed or purchased plastics in a home or automobile. 

So this is all just to say it’s been a wild and uncomfortable ride with my own health preoccupying much of my remaining energy as I wake up to what’s been happening for much of my life. I can experience and watch myself wake up with varying levels of cognitive ability and moods. Much like the character Taravangian… Sometimes he’s a genius and sometimes he is incredibly simple. While he has an amiable personality when his IQ is low, I happen to wake up both irritable and ignorant after a night of high exposure. 

A very large percentage of houses I’ve stayed in over the decades are abysmal from an air quality (for me) standpoint. This is not to blame anyone (well maybe the drywall industry) but rather a caution not to assume you’re safe just because your daily experience is normal. At least 25% of the US population has the same genetic susceptibility, but even those less susceptible are likely to have some effects from a water-damaged building.  For me, the effects were very very gradual. This means, even though you are probably opposed to hearing this, many of you are misattributing some kind of illness of yours or your family members to a non-primary cause.  Ignorance is our default. I’m nearly always looking at health-related content and I was ill-informed for something like 20 years. Even the allergists (2x) who both confirmed a mold allergy did nothing to warn me about living in moldy buildings. They were supposed to be the experts, but I was prescribed antihistamines and waved away.

A major difficulty in identifying this kind of problem or reactive immune system is that the symptoms can vary wildly. The main symptom going back the longest for me is simply difficulty sleeping, which starts maybe all the way back to my first move east...2001. For others, it might be depression, fatigue, or an itch. Eventually, I also acquired an inability to eat alliums and then increases in urination frequency became increasingly apparent. Despite the unusual cluster, I did not put the pieces together for years.  I thought each piece was unique. Only when symptoms started getting wild with nightmares, extreme anxiety, food intolerance, fatigue, hypothermia, dehydration, deep irritability, and paranoia did I start correlating the longer-lasting and more subtle symptoms. 

I was also fortunate to hear a few key anecdotes just as things were hitting a fever pitch of intensity. One of the most helpful public voices in the mold space, Judy Cho, describes her experience in which mold gave her mental illness including full-blown anorexia and aspects of bipolar disorder. Another popular podcaster, Michaela Peterson, recently triangulated her early onset rheumatoid arthritis along with various mental illness episodes to mold exposure. Her case seems like proof that there are many many misdiagnoses with very significant ramifications. She had multiple joints replaced and was medically tranquilized as a child...without remediating the offending substance.

It is very easy to not eat when you are nauseated, reacting to all food, and your thyroid is dropped to the floor. Of course, the medical system is not only not helpful but anti-helpful. The number of medical doctors and especially psychiatrists who might even be aware of this potential condition is vanishingly small. I wonder how many people think they have a psychiatric or neurologic illness and they are simply given a variety of drugs and returned to their moldy house or apartment? I feel quite fortunate to have found enough experiences that match my immediate situation and symptoms and while I don’t seem to have any permanent disability nor begun to identify with any incurable condition.

Below are some nice graphics about mold illness and its potential effects.

It is commonly misdiagnosed as:

  • Irritable Bowel Syndrome (IBS)

  • Post-Traumatic Stress Disorder (PTSD)

  • Chronic Fatigue Syndrome (CFS)

  • Fibromyalgia

  • Attention Deficit Disorder (ADD/ADHD)

  • Somatization (example: Hypochondria) 

  • Autoimmune Disorders

  • Depression and anxiety

  • Allergies

So this is the world I’ve been in. Because of the VOCs, I avoid time sitting down at home, but outside of the house, I am doing a lot of reading and listening as I try to map a possible path forward. I plan to wet vacuum and hot carbon clean my carpets a few more times - this helped significantly the first time and to get more heat and sun as the seasons change down here.

Almost none of the mold resources mention this but one natural way to feel better is to increase alpha-melanocyte stimulating hormone (a-MSH) which we naturally get in the sun.  It’s a potent anti-inflammatory.  You can also buy it in a vial.  

I hope this essay can be a bit of a public service announcement that can reach a few people thinking they simply have adult onset allergies, or are wrongly diagnosed with something proposed as congenital or unremediable. As of 2020 and later there are now reasonable treatment protocols that work once we can extract ourselves from mold and VOCs.  If this is relevant for you or someone you care about please forward and or reach out to me and I can share more resources.

Some of the best resources on this topic:

https://www.nutritionwithjudy.com/cirs

Biotoxin.com

https://www.survivingmold.com/resources-for-patients/save-vip/additional-uses-of-vip

https://www.survivingmold.com/resources-for-patients/treatment

https://www.amazon.com/Beginners-Guide-Mold-Avoidance

]]><![CDATA[Vitamin D, The Elephant in the Closet]]>https://www.revfire.us/p/vitamin-d-the-elephant-in-the-closethttps://www.revfire.us/p/vitamin-d-the-elephant-in-the-closetThu, 02 Feb 2023 20:48:40 GMTJohn Campbell one of the calmest and sanest voices around COVID has made a video recently that makes me feel both distressed and validated.

It’s 14 mins (Video here). It’s based on this study here.

I like how he points out all the English-speaking countries are silent on this topic…actually worse - they use their authority to protect patent medicines.

He gets emotional in the video as I too am. It’s hard to stomach that we all got dragged through an avoidable car wreck of manipulation and mismanagement.

How much stress and how many lives lost were so so simply avoided?

Can you imagine the scenario of ensuring vitamin D adequacy across the globe? Using the fast-acting form in COVID wards with no lockdowns, no long-Vaccine, no sudden heart attacks etc1.

I bet your mind will not let you really imagine. We are all vested in feeling like we can trust our fellow man, our leaders, and our institutions. Without those life is very very uncomfortable.

The alternative that did not happen would “cost” on the order of 10$ per person per year. Let’s be grand and say $20 pp py. Everyone would buy their own and the real costs would be a GDP drop from reduced admission from a variety of other conditions.

Let that sink in: $20.00 - $60.00 for the three years subsequent.

Cognitive dissonance yet?

Do we know why Vitamin D was informationally banned and blacklisted?

Does the eluded-to hypothesis seem plausible?

“the FDA may authorize unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when certain criteria are met, including there are no adequate, approved, and available alternatives.”

(source: The FDA)

Do you still trust your doctors or politicians? It just so happens that on this particular issue, the democrats are the party opposing physiological reality.

I am not advocating a preference politically, but team blue, having aided in the choices it did, has ceded all claims of superiority in the realms of science, logic, intelligence, or moral righteousness.

It is existentially worrisome to wonder at motivations or ignorance around this. I’m not sure which I prefer. The acts of omission or commission, in either case, are astounding.

Human rights tribunals seem appropriate to me, but unfortunately, I suspect what we've experienced will be nearly forgotten in the "emergencies" to come2.

Here’s the article I wrote on Vitamin D after telling everyone I could what I was doing for the years prior. You don’t even have to read it. Just implement the stupid simple solution:

Get your blood levels of vitamin D to 50ng/mL.

It’s not just for COVID. It’s a massively important signal from nature telling your body that plants and animals are going to be bountiful in your environment so you can spend more energy on repair.

You can get tested without your doctor’s approval...I guarantee it’s worth 50-100$ for a couple of tests.

Ideally, get as much as you can from the sun in nonburning sessions.

Add in cod liver oil and or 10,000 ius/day in olive oil as aids.

But my doctors say…yeah they will say you are not deficient or even worse you are “normal” and did they say how much time they spent researching the topic? How much time the mechanism was discussed in medical school?

Please please ask anything like that.

Ask about the physiological mechanism.

Ask them if they know any implications of evolution on medicine at all.

Ask them if they even think human life is worth preserving.

I dare you to ask any question of your MD which explains the logic of their position on this or anything really.

When you do, let me know how that goes.

1

Of course, an even better scenario might have been not to fund the manufacture of the virus in the first place. Were you aware that lab leak is now a leading origin theory? (Source: Bloomberg). It is almost hard not to believe in a major conspiracy, and even without some crazy Fauci-Bilderberg plan to cull the population at least there seem to be a lot of less grand conspiracies to cover up masses of corruption and incompetence.

2

I will sound ever kookier saying this bit, but it’s quite clear to me that many many educated liberals actually want much fewer humans on earth. Some of you reading this included. I’m not exactly judging, I know now that we confuse our own misery with the state of the world. It’s a trap we all default to. That said this means a lot of power and wealth is pro-all the things I would rather not, and yet seemingly will, live through ie: famine, pestilence & global war. Am I totally batsh!t crazy…maybe, probably so…but also consider the last century…and the current geopolitical news.

]]><![CDATA[Psychedelic Singularity ]]>https://www.revfire.us/p/psychedelic-singularityhttps://www.revfire.us/p/psychedelic-singularityFri, 20 Jan 2023 09:11:34 GMTThere's something happening here

What it is ain't exactly clear

Buffalo Springfield

I happen to be paying lots of attention to the AI news and tool deployment. To jump a lot of pondering to a tentative thesis and ramblings…

Awakening

It turns out we are making great strides on the path to godhood relative to all we’ve experienced thus far. We both do and do not have a choice in the matter.

As individuals and groups, we can choose to stay in existence with this turmoil and metamorphosis, turn away into distraction, or potentially even exit the field of being.

It seems that the nature of the universe is structured to reproduce its reproduction, and sentience is somehow part of all this doing. I think of bubbles blowing more bubbles in a fractal-like manner. Soon enough, our boundaries will become somewhat blurred with each other and with stuff in space.

We already have a limited sense of what this is like when we operate a machine or tool and begin to understand ourselves as it is us in space. Think of driving a car or using any tool or instrument that becomes routine below consciousness...your brain starts treating it as self to some degree.

We also know how it feels to be in sync with another human or even a group. Now imagine our cognitive powers increasing with weirder instruments and machines to play or to wear and with much greater capacity to emotionally and computationally link with others.

We have the illusion of having ideas when our ideas manifest from our subconscious or deeper a recombination or regurgitation of other ideas we didn’t create. We often assign them property rights and feel something when we are praised or validated. I write this document with ideas that are mine and not mine.

Yet, Like all things in my life, I do not choose the contents of my consciousness, and it seems that holding on tightly as if I did is an easy way to get stuck and distracted from the benefit of being present and inquiring into what we really are.

I don’t imagine this unfolding process will stop without great suffering, even possibly horror. Still, I hope that my remaining fears are projections of the cognitive systems built as hypersensitive to threats.

Yet in that fear, I am on a mountain where I see a tsunami “far” in the distance. I don’t know its speed, and I sense that running will not increase my safety. Calling others which may ease my sense of aloneness, will ultimately do little to change our fate.

The Universe Is More Open Than We Can Imagine

Towards the future, we already have great social fear projected into our cinematic art and into those we listen to on the news and in various media. Is something like the terminator or matrix more of a commentary of the times it was produced or the actual future? Just the other day, I was worried that billions would starve. I’m worried about witnessing that and being returned socially to states of rigid authoritarianism and deprivation.

I’m worried about the death knells that ring when the collective is triggered into fight or flight. I project my fears into my attention on the world. That’s what fear does. And then I even found myself judging myself for not being productive and trying to immediately figure out how to win in this new race to produce value with the new tech tools, and it took me a minute to realize this, too, is fear.

I might know better. In so many things in life, we are the passive recipients of our fortunes, and this is, in some sense, no different.

I’m a bit manic with the sense of potential. It seems too big. People are solving problems and psycho-emotionally waking up. I sense that the ones that find randomly placed gold mines will more rapidly than ever realize the folly of hoarding. And if they don’t, the “problem” tactically will be to coerce them prosocially.

Perhaps many of us will use our new free time for connection, enlightenment, or artistic expression, which are inherently therapeutic. Any lone trillionaire will find themselves unwinding their trauma simply by imitating the rest of us. I don’t know all the kinds of strategies we will invent but realizing the universe is abundant is very near at hand.

Perhaps you will balk at what I’m saying but let me paint a quick picture:

Each of the below is at least one dimension of nonlinear performance gains.

  1. Hardware developers are using exponentially more powerful tools to produce much more powerful computational hardware tools.

  2. The software folks are using their own AI to exponentially improve the performance per computational operation…so far.

    1. This is really important because, very quickly, energy could be a constraint.

  3. The above is working to deploy the tools broadly.

    1. A nonlinear explosion of existing coders is already downloading and getting competent in the new tool interfaces.

    2. New coders will be entering the market with massively reduced timeframes for learning and applying.

    3. Non-coders will shortly after that have the ability to no code solution engineer, so anyone who wants can learn to contribute.

  4. Physicists, mathematicians, geologists & engineers who work on energy will be able to use the above dimensions of cross-multiplying hyperbolic improvements to design and produce lower-cost energy products to further the design and production of all of the above inputs.

And so I expect massive energy production breakthroughs in all domains in 2023, 2024 and beyond. I suspect this means deflation, massive deflation.

Why? Because ultimately, dollars and debt are claims on energy and energy production is about to skyrocket... while in the short run, the debt outstanding will keep collapsing...Lots less claim vs lots more energy... One risk is that the bots will ultimately consume all the energy...but savings in other domains may make up for it.

fingers crossed ; )

I’m expecting everything will be restructured in light of this explosion, including our political arrangements, property rights, and even our biology. As stated above, our boundaries will be pretty blurred in all this and, perhaps, our sense of time. Weirder than weird from here on out.

That's my guess/understanding at the moment.

I’m not sure what can really be done or needs to be done.

All of those who can are well into executing this thing. I’m happy to connect and listen to anyone who receives this.

I know this is quite whacky, and I’m happy to be laughed at now and when I’m entirely wrong instead or approximately right in 6,12,24,36 months.

I sense that the most appropriate thing to do might be to celebrate with others the end or the beginning...whatever this is.

]]><![CDATA[Modern Holy Grail! v1]]>https://www.revfire.us/p/modern-holy-grail-v1https://www.revfire.us/p/modern-holy-grail-v1Sat, 22 Oct 2022 22:08:43 GMTModern Holy Grail! Eat Carbs, Lower Stress, Lose Fat!

I had to write this up because many of my friends and family are now interested in this Brain Energy book which will be out shortly: Brain Energy.

I totally appreciate where the guy is going and strongly agree overall with his unifying disease model, he just doesn’t seem from videos and the blurb, to have the better alternative to a keto diet in awareness. He like so many seem to think PUFs are fine while glucose and fructose are the culprits of insulin resistance. I suspect his references will support the combined disease model but not his full dietary recommendations.

Moving away from the standard American diet is so amazing that everyone trying a diet that gets away from it a reasonable amount feels better get super excited (partly from the adrenaline), and then feel like they have arrived. I get it, I’ve been there.

I still need to add on some pro-dopamine hacks that is why this is v1. If you want to see those let me know.

Don’t do Keto...better alternatives exist

Many people are demonizing sugar and promoting Keto these days, so I suggest keeping some of their helpful ideas and reject others.  Unfortunately we are still strategically deceived.  The pharmaco-medical complex simply does not want to give us readily available inexpensive compounds that will promote health nor address the underlying food issues accelerating mortality.

Most MDs, even the ones really trying, are inadvertent accomplices.

  • Focus on macros is not insufficient and likely unhelpful. 

  • If you eat only potatoes you will lose weight. This is not the only way, but it counters the Keto oversimplification immediately.

    • Partly because it’s boring, but primarily because potatoes are full of potassium, gaba and other nutrients that aid the food in getting into cells in the brain which promotes satiety.

  • Fructose in the context of fruit is wildly, yep wildly different from high fructose corn syrup...which has no paired potassium and no other nutrients or signaling molecules

    • People seem to get so angry when you point this out IDK...maybe because they are not eating sugar ; ) 

  • If you increase Omega-6 while on keto you are dramatically working in opposition to health promotion as if the stress hormones were not enough. 

    • Short fasting and short term pulses of stress hormones from exercise are likely beneficial, but it rapidly goes against us when we already have loads of other stressors.

Catabolic hormones - cause diabetes, stress not fructose is the culprit 

Stress hormones: glucagon, cortisol, adrenaline, norepinephrine 

“Experimental evidence suggests that sympathetic hyperactivity may be a pathogenic factor for type 2 diabetes as well as for the occurrence of diabetic complications. Interestingly, dopamine agonists, which exert multiple actions including a decrease in sympathetic activation, have recently been found to be of benefit in the treatment of type 2 diabetes.”

“Glucagon produces insulin resistance. Glucagon-induced insulin resistance promotes type 2 diabetes and diabetes associated with glucagonoma. Further, glucagon-induced insulin resistance aggravates the metabolic consequences of the insulin-deficient state. A major metabolic effect of insulin is the accumulation of glucose as glycogen in the liver. Glucagon opposes hepatic insulin action and enhances the rate of gluconeogenesis, increasing hepatic glucose output. In order to support gluconeogenesis, glucagon promotes skeletal muscle wasting to supply amino acids as gluconeogenic precursors. Glucagon promotes hepatic fatty acid oxidation to supply energy required to sustain gluconeogenesis. Hepatic fatty acid oxidation generates β-hydroxybutyrate and acetoacetate (ketogenesis).”

“Chronic glucocorticoid (GC) exposure in humans is well known to result in whole-body insulin resistance and obesity.”

Natural Anabolic hormones, hormones that promote healing: testosterone, insulin, growth hormone, DHEA etc.

A note on Insulin, Glucagon & Gaba: Insulin does not cause insulin resistance - Glucagon does. Almost everyone’s base model is wrong and has been for 40 years.  Pharma companies know this and after getting as much money from insulin as possible, have switched to supplying GLP-1 inhibitors, so soon enough we should see MDs catch up. 

See: Robert Unger, Glucagon receptor inhibition normalizes blood glucose in severe insulin-resistant mice 

Insulin racket: Diabetes patients sue insulin makers for ‘pricing fraud’ - The Washington Post - what they don’t say is that the science was also distorted for 5 decades to promote insulin sales!

GABA (gamma aminobutyric acid) - An OTC non-pharma inhibitor of glucagon

“Our data show that GABA is rapidly absorbed and tolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal secretion, suggest potential therapeutic benefits for diabetes.”

“Oral gamma-aminobutyric acid (GABA) supplementation increases growth hormone (GH) serum levels and protein synthesis.” 

“Besides, various pharmaceutical properties of Gaba on non-neuronal peripheral tissues and organs were also reported due to anti-hypertension, anti-diabetes, anti-cancer, antioxidant, anti-inflammation, anti-microbial, anti-allergy, hepato-protection, reno-protection, and intestinal protection. Therefore, Gaba may be considered as potential alternative therapeutics for prevention and treatment of various diseases.”

DHEA

“DHEA therapy compared with placebo induced significant decreases in visceral fat area (–13 cm2 vs +3 cm2, respectively; P = .001) and subcutaneous fat (–13 cm2 vs +2 cm2, P = .003). The insulin area under the curve (AUC) during the OGTT was significantly reduced after 6 months of DHEA therapy”

“DHEA reduces adipose tissue mass and inhibits the proliferation and differentiation of adipocytes”

HGH

“In summary, the predominant effect of GH in the adipose tissue is the stimulation of lipolysis....Unlike in the adipose tissue, GH induces free fatty acid (FFA) uptake into skeletal muscle”

Testosterone

“Low testosterone concentrations at baseline predicted higher insulin resistance at follow-up, but high insulin resistance at baseline could not predict low testosterone at follow-up.”

Active Thyroid (triiodothyronine): Thyroid hormone is catabolic to fat while being healthfully anabolic (restorative) to the heart

Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy

Serum thyroid hormone levels may not accurately reflect thyroid tissue levels and cardiac function in mild hypothyroidism

“Thyroidectomy alone led to cardiac atrophy, severe cardiac dysfunction, and a dramatic loss of arterioles”

Thyroid hormone as a therapeutic option for treating ischaemic heart disease: from early reperfusion to late remodeling

Thyroid hormone and "cardiac metamorphosis": potential therapeutic implications

Thyroid hormones and cardiac remodeling

Thyroid hormone and cardiac repair/regeneration: from Prometheus myth to reality?

“TH can induce cardiac repair and (or) regeneration by reactivating developmental gene programming”

Thyroid hormone action on intermediary metabolism. Part I: respiration, thermogenesis and carbohydrate metabolism

“T3 directly stimulates mitochondrial respiration and the synthesis of adenosine 5'-triphosphate (ATP)”

Thyroid hormone at supra-physiological dose ... improves cardiac function

“TH treatment partially reverses cardiac dysfunction in rats with old myocardial infarction by favorably changing cardiac chamber geometry and expression of myosin isoforms. Thyroid hormone, unlike current treatments, appears to be a paradigm of therapeutic intervention which aims at restoring cardiac geometry and may prove new effective treatment for heart failure.” 

Various:

Regeneration of Pancreatic β-Islet Cells in a Type-II Diabetic

Strategies of Functional Foods Promote Sleep in Human Being

]]><![CDATA[Omega Point]]>https://www.revfire.us/p/omega-pointhttps://www.revfire.us/p/omega-pointTue, 11 Oct 2022 02:10:33 GMTPurpose?

What am I trying to say with these articles and eventually a book around Metabolic Morality now I’m calling Revelation of Fire?  A famous author suggests that non-fiction authors try to work from the end point and work backwards.  This was immediately helpful because my feeling every time I write an article is that 10 or more ideas emerge and the potential end grows further and further away. I have a mental image of myself and my huge mouth trying to swallow the world and I’m wondering the whole time if the effort is not a bad idea. Some have called this the combinatorial explosion.  Alas I am seeking to introduce a bit of constraints, a knife and fork with which to break it all into swallowable bits.

An Early Aside

As a quick aside, I plopped down to write this and thought to call it the “Omega Point” fairly literally as “the end point” not realizing the history behind the term. Apparently, “Omega Point” comes from Teilhard de Chardin who was a Jesuit Catholic priest and paleontologist! If you didn’t know that combination could exist we feel the same. To reconcile his two seemingly opposing passions or loyalties he tried to create a synthesis between Catholicism and evolution. It seems to have been a very noble effort and yet for that effort, or more precisely for talking about it, he was exiled to China! Yet his ideas caught on and many famous thinkers are influenced by his work with some conception of a soon arriving transformation.  The most popular of these in our current time is called “the Singularity” coined by Ray Kurzweil and influential in Silicon Valley. 

Foci

Return back to my foci, my aim in all my current writing is to present an argument about how energy throughput in the human organism as well as through the economy or society is the critical variable for things like health, wealth and social harmony. I am deeply biased by this view and I suppose I ought to simply admit this at the get go. I can only see a few of the ramifications, but the more I try to explore the more interesting they seem. I have predominantly been looking through this sort of lens into physiology, but have ever more been looking at societies, religions, businesses and economies and the energy throughput view seems quite instructive.

History

The best evidence for my overall thesis comes from history and historians. Prior to trying to understand and validate the impact of energy on society, I thought I hated history. Yet historians have really gone deep to dredge out the better explanatory factors for the rise and fall of civilizations. With just a little searching, the evidence flows overwhelmingly as to the relationship between the energetic status of societies and their success. The material histories of most cultures we know existed in times and places favorable to human flourishing. Optimal climate for agriculture seems to be the key variable. The capture of consumable energy drives social strength, political liberalism and innovation. From those we can derive things like guns, and steel while germs too increase with the extent of trade and urban density. Relatedly, the ability to resist germs is significantly related to the health of the population. Favored authors in this niche include: Ian Morris of “Foragers, Farmers, & Fossil Fuels”, Philip Jenkins of “Climate, Catastrophe, and Faith”,  “The Evolution of God” as well as “Nonzero” by Robert Wright and Vaclav Smil of”Energy, and Civilization & History”.  

Economics 

While most economists have abstracted energy and money out of their models, these factors can be added back for absolutely critical insights into the real world. At least one economist, Steve Keen, is doing this kind of work and pointing out that most of real economic growth comes from increasing the economy's use of energy over time. He suggests that explains 85% of all growth, and I would imagine the remainder is still from energy but would from efficiency gains. Thus all economic growth is from or is equivalent to energetic throughput.

Inflation - in an energy focused model inflation would have different meaning.  It might be that we always need to clarify the difference between monetary inflation to include private debt growth and real price increases from energy supply shortages. This is a sort of geopolitical cycle where the monetary policy increases the base of the money supply and to a large enough extent this undermines the stability or will of the global energy producers. 

Interest rates

Interest rates must have some relationship to energy which is not very well articulated by mainstream economics. My current sense about interest rates is that higher real interest rates are required to refocus economic efforts to things that matter the most such as: the energy sector.  With increased rates a higher proportion of income will find its way to investments that are able to yield higher returns and it seems likely that many of these will be related to delivering increases in energy.  We can also note that the energy (petroleum) price increases are a, if not the, prime driver of inflation. American economic exceptionalism is perhaps able to continue only so long as the US, or the west more broadly, is able to increase its per capita utilization of energy. After the 70s it really started to slow down, we stopped building nuclear plants and the middle east raised the price of oil. In recent years it has picked back up with fracking, but it's in serious jeopardy with the luddism around nuclear power and the twisted sense that we should actually remove people from the Earth.

Western (especially American) Vulnerability

Central to my view is that America’s real economic Achilles heel is its complete disregard for human physiology. Many of the largest, most powerful sectors: defense, petroleum, pharma & medicine, finance, agriculture, food supply, and technology are receiving rents for undermining the physiology and cognition of their customers and employees. Profit maximization such that it kills the society is very short sighted to say the least. Yet, the incentives are rigged to drive these outcomes. From my perspective there is really no specific person to blame...so perhaps the rules of the game need to be reworked to reduce myoptic optimization and emphasize biological, ecological, full system constraints along with longer term optimization. I’m fairly confident there must be many better ways to organize.

In a framework in which increasing energy throughput is necessary for economic growth, we can evaluate the real impacts of various environmental policies. Relevant to the existing geopolitical situation, a rapid reduction of the use of petroleum without a viable alternative will cause a severe recession or depression with many unforeseeable consequences.  That said, further immiseration of the poor is almost guaranteed.  

Science

While cumulative science is quite a novel institution in the modern world, its organizing mechanisms are not nearly as innovative as many findings.  The same kind of behaviors that compel humans to organize and attend church are at work in the various disciplines. In many domains validating new “truth” is avoided as long as possible prior to acknowledgement of the overturn.  New findings and theories dramatically upset the status and incomes of those who are fully aligned with the previous paradigm. While the people and conflicts are more diverse are more heterodox, the battles within academia are not so different than those between the Catholics and Protestants after Guttenberg.

Business

Money as a store of value is equivalent to money being a claim on future energy.  The most basic way to say the same thing is that you can use money to buy food, heat & shelter.  Money; therefore, is a kind of accounting of potential energy. Profits are obtained by dynamically increasing or maintaining financial throughput, which should on some level mean they are successfully increasing their share of potential energy.

Let’s take Apple which is known to have a large account of cash. On some really basic level they build a device whose cost to build, ship & deliver is at least 50% or less of what it costs retail and then we use those devices en masse to more efficiently live. Many may only use them to purchase entertainment more easily but many will also use Apple products to build businesses. The company is making money (storing and using energy) by increasesing the speed at which others can do the same.

Perception / Phenomenology

The experience we have and the world we perceive safe, benevolent or unsafe, malevolent is predominantly a result of the same: energy flowing through systems perceiving and calculating our body budget. As energy throughput reduces, humans self-organize or cohere like steam becoming water, in fact it’s not quite a metaphor because the related behavior is based on the same fundamental physics. We might call this condensation or congelation.

Personality & Morality

The tone of a person or culture and thus the morals and religious behavior is determined by the energetic throughput aka metabolism of each respectively.  This is probably the hardest nugget for most of us to buy in.  As far as I can tell most people really identify with their current set of values or morals and don’t see how they might change in differing circumstances or physiological states. We are in some sense meant to be blind to this...this is perhaps the largest “mote” in our eyes.  Yet taking it out we can clearly see how we are all made of the same stuff despite our current views and preferences.  

In sum  

A system that is increasing energy throughput will be engaged in searching for new energy sources to exploit. While having and finding energy sources the system is fundamentally open...this openness is to novelty, variety, new DNA, to new microbes, new configurations, new shapes and more. It looks like exuberance, seeking, experimenting, growing, making peace, not being fussed, sharing and doing for others. 

]]><![CDATA[Long COVID]]>https://www.revfire.us/p/long-covidhttps://www.revfire.us/p/long-covidTue, 27 Sep 2022 03:39:50 GMTFor all my friends and friends of friends who might still be suffering from long COVID. I pass on to you things which I have not tried because I have been lucky not to have to. These are ideas which clearly seem in line with my metabolic/bioenergetic view of the world which is to say they are highly plausible. They are also very low risk and low cost.

The best resources I’ve found and I will thus basically copy from is here:

Butterfly Method

I suggest you just read that and follow his/her logic and suggestions, but I’ll also try to abbreviate or simplify below.

What I found most sad, interesting and consistent with what I’ve previously written about is the vulnerability of younger generations of women to long COVID.  Here are the charts suggesting a link from the above paper:

It might not be that thyroid is the contributing factor, but my evolutionary thinking and experiences lead me to find that idea highly plausible as at least a, if not the major factor. It could be that women are intrinsically a bit more metabolically sensitive to stress broadly, or perhaps behaviors unique to modern women like chronic undereating, taking birth control or simply avoiding pregnancy and nursing are impairing the thyroid. I have good reasons to believe in both and no good answer for the balance of the causal weighting. 

Both birth control and PTSD flatten circadian cortisol curves, increasing stress at rest and reducing full stress response to events like infection

(source1, source2, source3)

Muted cortisol seems to be highly predictive of long COVID:

 “Of all the factors, abnormally low cortisol levels were the factor that really differentiated the long-COVID patients from the healthy controls.” (source)

What is the relationship between PTSD, Thyroid & Cortisol I do not yet know.

Regardless and pragmatically here is an approach to postCOVID consolidated from the butterfly method blog. You can use the symptoms on the blog to see where to start or just do all in parallel:

  1. Fix Intestinal dysbiosis:

    1. Probiotics & Prebiotics

    2. Monolaurin a saturated fat and gentle soap/antiviral

    3. Melatonin & Niacin, Niacinamide (add NMN if you are following anything I’m writing about anti-aging)

  2. Assume thyroid dysfunction and fix or mitigate it

    1. Iodine and retinol are thyroid precursors

    2. Iodine - 

      1. Create “blue iodide” - mix normal Lugol's iodine with starch (amylose)

    3. Vitamin A/retinol (or get it from liver)

      1. Many people do not convert beta carotene to retinol 

      2. One can overdue retinol, increases in retinol dramatically increase the need for vitamin D, K & E

    4. Selenium 

    5. Zinc and copper (copper is dense in liver tissue)

  3. Assume Iron Overload

    1. Give blood

    2. Chelate iron 

      1. Curcumin

      2. Thiamine/Benfotiamine (my addition, source)

      3. Inositol hexaphosphate

    3. Manage Iron

      1. Retinol, Zinc, Copper, Magnesium, Selenium

  4. Me

    1. Try/Add Methylene blue, especially Methylene blue and sun exposure (within a few house of ingestion), NMN (a form of Niacin), creatine, supplemental desiccated thyroid, sun exposure, fresh orange juice

      1. Everything that increases cellular energy is probably good for the immune system

      2. Pushing down cortisol at night with ashwagandha, astragalus or apigenin is also worth a try

Sources:

Long Covid - Recover via Fasting / Autophagy | Facebook

Long covid—mechanisms, risk factors, and management | Southern Health

Benefits of Niacin (Nicotinic Acid), Miracle supplement?

(My prefered probiotic provides oxytocin) Even dead L. Reuteri boost oxytocin and bring many benefits | Ray Peat Forum

The Team of Doctors and Biohackers Who Seem to Be Successfully Treating “Long Covid”

Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro | Scientific Reports (www.nature.com)

Role of methyle blue in the management of mild, moderate and severe COVID-19 disease

OSF Preprints | Sufficient niacin supply: the missing puzzle piece to COVID-19, and beyond?

What is NIATONIN? - audio from Dmitry Video with transcript

Notes: "The Niatonin Protocol" To Heal Inflammation (Covid, Long Haul Covid, Vaccine Injury, Chronic Illness) – A Masterclass by Dr Kats - katrinah.com

Apple pectin for the reduction of niacin-induced flushing (Aspirin is also useful for the same and is also antiviral)

People Thirsty to Reverse Their Coronavirus Vaccination Love This Wacky 'Treatment'

This article was a critique - They are so sure about physiology and the motivations of the biohackers - I absolutely do not agree but here is the TLDR.  IMO this is for those who wish to stay helpless in all this mess:

“A few people have built entire businesses centered around these products and services. “It’s all bunk,” Hotez stressed. “But it has made money for these people.”“Any product or service that claims to undo or reverse the impact of the vaccine is based on a lie,” O’Connor added.

(me: Whomever O’Connor is the idea that we “cannot undo vaccine impacts.…i.e…inflammation” is kind of like saying we will never fly not realizing its 2022 it’s happening all the time everywhere so huh?) Let’s hope someone dramatically misquoted the person.

Note: I have not included doses and sources. Happy to discuss with my friends and family currently in 4 continents. I’m currently in New Zealand which is known to be deficient of selenium and iodine immediately…and treats Melatonin like a street drug. Cases will vary. Maybe a good rule of thumb is to find out the government daily recommendation and aim to take 2 - 4x for a while for the minerals above. Overdoing selenium and other factors is not good despite how critical they can be.

]]><![CDATA[Interesting Interest Rates]]>https://www.revfire.us/p/interesting-interest-rateshttps://www.revfire.us/p/interesting-interest-ratesSun, 25 Sep 2022 03:53:40 GMTThis piece is a tidbit focusing on market possibilities that western countries have not seen for a generation or longer. Personally, I simply thought interest rates would never be lifted in my lifetime and asset values would continue toward the sky as long as I could look up, and yet that which could not persist finally did not persist. As well we will now all pay only as early as we were forced for our collective ignorance.

The short run now looks bad, the medium term catastrophic and for whomever of us is left the long run will likely return a cycle of growth and expansion from contractions we are currently initiating.

For decades the financial industry has been selling a narrative about the return from long term investments in the market. The government has joined that chorus and added assurance of their ability to manage all liquidity crises and debt cycles with monetary policy. They will deliver liquidity when the market cannot or so the thinking goes and we the people have demanded easy but false answers to our porblems. I belive we have no look far enough back or wide enough around for alternative possibilities. 

In short, our leaders suggest they have it all under control while we bury our heads and believe eveything will be ok. 

ZIRP (Zero Interest Rate Policy)

Low interest rates make everything seem like it’s better than it can sustain and not knowing any better we have been duped by false signals. The Fed and politicians in favor of ZIRP have ignored or are unaware of the costs of such and the future hell they will always imply.

If I relate interest rates to their fundamental source: trust, we get a litte more perspective. There are some amount of criminals in society and yet, we do not want to be fully closed to others, implying very high even infinite interest rates. Neither do we want to be nice and skeptical (Zero interest rates) to the point that we become prey to the worst people and the worst kinds of coercion.

ZIRP from my point of view is akin to asking the devil to dinner, because he swears if invited it will be a grand feast. Without our hackles raised we assume we have a shared concept of whom will be eating and uopn what. Our long but limited expereince has led us to unknowingly become turkeys who are charmed by our socio-political benefactors.

Exemplary Japan

Very few people outside of finance seem to know that policies in the US (and thus 70+% of the globe) have lagged Japan by a decade or two. They went to zero interest rate policy (ZIRP) faster and harder than any other nation from a peaks in 1981 and 1990. Here are the interest rates set by the Bank of Japan (BOJ) over the last five decades: 

Japan marched towards their zero interest rate starting in the early 1980s and within a decade they created one of the world's largest asset bubbles in both housing and financial assets. A massive bubble in housing and financial assets...does that sound familiar?

Both of those markets peaked and then popped from around 1990 - 1991.  The Nikkei can be thought of as the Japanese equivalent to the S&P 500.  Below is the Nikkei price level over time with data from left to right moving us towards the present. 

Notice that the Nikkei has trended negative from January 1990. This is a famous financial bubble pop coincident with a policy rate hike from 2 - 6%. Through 1992 the market was down about 50% and then continued down another 50% of the remaining value over the years 1992 to 2010.  From 1990 the Bank of Japan lowered rates from 6% to 0% over 5 years, but the market did not return.

Similarly but slower the real estate market also cratered for most of that time:

Notice that the real estate market took a few months to years to begin its much slower but similar magnitude decline. The median home price halved over the 17 years from 1993. Despite effectively zero interest rates from 1998 onward the market never rallied during that period. 

Policy Mimicry

Below are US interest rates over recent decades. We can see that we toyed with ZIRP for the first time in 2002, where we reflated the bubble in tech, pumping it into housing. Housing which inflated dramatically and then popped or fell over in 2008 after the Fed raised from essentially 1% to 5% from 2004 - 2007.  This is why some people blame the Fed for the global financial crisis

...it is not an unreasonable position. In the current Fed’s defence they have only so many tools, and concencus seems to have encourage the interest rate decline.

After significant consumer price inflation from both increases in money supply and decreases in goods available, the Fed is now reversing 40 years of unidirectional policy.  So far we’ve seen the S&P 500 lose about 30% over 8 months while rates have moved from 0 to 3.25 percent and the Fed promises evermore more hikes. It looks to me like the same dance. Do we think US housing might come to look like Japan? 

I would bet on it. 

Correlation, causation and mechanism

What I’ve shown are some loose correlations. I’m fairly confident that interest rates driven by central banks have enormously outsized effects on the regulated economies. I feel this way because the mechanism (theory) is corroborated by data ( empirical findings). It’s not certainly right, but that combination is a higher standard than much of what I typically see in both health and economics research and then all the blah blah nonsense always supporting the status quo and vested class of interests.

There are many mechanisms describing the relationship between interest rates and asset prices but we should look at two. One for each large asset category: stocks and mortgages. 

Stock Valuations

Stocks are valued multiple ways and those valuations are influenced by interest rates in multiple other ways, but let’s look at 2: NPV and Corporate Finance. 

NPV 

Net Present Value is one of many methods to value stocks or really any asset. NPV says that the current value of an asset is equal to the future cash flows discounted by the cost of capital (the interest rate) for each period. Let’s learn from extremes. Let’s say we have 0% interest over 5 periods of paying 10 units. The NPV is simply 50. If the 0 goes to 10%; however, we have an NPV of 10/1.1 + 10/(1.1^2) + 10/(1.1)^3 + 10/(1.1)^4 +10/(1.1)^5 = 39. This is a 22% value loss from simply a raise in the interest rate aka discount rate. For most stocks this value is determined by the expected earnings per share (EPS), but something very sinister is baked into the whole stock market by incentives, policy, culture and law.

Stock Buybacks

Stock buybacks are when a company uses cash or debt to reduce the amount of shares outstanding. They simply purchase them at the market price. This is a way for CEOs to increase earnings per share, EPS, and maximize shareholder value, at least in the short run, without really increasing real earnings. Reducing the denominator (the count of shares) even makes future potential earnings increases more impactful.* 

*Note that financial engineering like many costs cutting exercises fail to increase throughput. Through put is the link between physiology, business and economics. Being ignorant of the importance of metabolism or throughput we allow corporations to do the equivalent of insane weight loss. The doctor says loosing weight is healthy lop off an arm and voila better health right? Unfortunately most of the experts in most domains are obsesed with the wrong metrics and leading everyone to make absurd decisions.

Investment websites say that stock buybacks should happen when a CEO believes the market is undervaluing its stock. However, the use case is much broader, more related to the costs of capital, and much more likely to occur when valuations are already stratospheric. That is when interest rates are nearly zero. 

The cost of equity capital is something like the expected earnings growth or dividend per share. If we simply think of a dividend company, one without really trying to grow, this company returns all its capital to investors. For this company both equity and debt are sources of capital for the company to operate. If debt is essentially free then a CEO is almost obligated to reduce the capital costs and increase stability of access to capital by buying back stocks. The CEO uses debt to reduce the outlay required or expected by dividends. With consistent total earnings this makes remaining stock values go up with reduced shares. 

As rates have been dropping, this has been happening across the market...for decades. From the outside it’s nearly impossible to know which companies are growing from real, unbaked earnings and which from some kind of real improvements. The overall market is likewise going up, but it’s not a chart that considers the potential reductions of outstanding shares. Things seem good when the market is up...but perceptions can be quite misleading.

Imagine you are a CEO or CFO incentivised with huge stock options as part of your package and the government reduces interest rates and thus the cost of capital by a non trivial amount. For both you and the current cohort of investors you should, you must borrow as much as possible and buy-back as many shares as possible. Maximizing shareholder returns is your number one objective, and that is how you do just that. On some level what you are doing is realizing the stock value of the company by trading it to the debt risk counterparty. If you are a big company it looks like you are sound, maybe yes, but maybe that will turn out to only be true when capital is cheap. You actually sell that soundness which is in some sense just cashing out the trust of goodwill built up by the firm's history of acting reliably for owners and customers. 

Systemically lowering rates bakes in a future crisis or a profound bear market. If ever rates were to return, the capital costs funded by debt would dramatically increase thus increasing the costs of capital to the firm. To reduce those costs they will either have to pay down debt or replace it with equity causing the opposite dynamic of further suppression of stock valuations.

From a theoretical perspective companies should likewise abandon all activities that (for the equivalent risk) do not pay the market rate..which if done well after a material rate hike should cause many activities to be shuttled. Many companies will even find that they should not even exist and their new realized asset values will materialize only through default and bankruptcy after their shareholders have been wiped out. 

Oops!  Maybe we should have made the requirement...maximize long term or full credit cycle shareholder value. Bad corporate governance and bad public policy seem to go hand in glove.

The Housing and Mortgage Markets

A 1,000,000 priced home bought based on 3% interest rate has equivalent monthly payments as a 680,000 home based on an 6.3% interest rate. That's a 32% change in the price based on the ability to pay monthly which is what both banks and consumers base purchases on. That reduction does not take into account the lost jobs from a massive market slowdown caused by reduced building, reduced consumption and overall recession...or depression. 

We will not see housing prices reduce as fast as stocks because they are very illiquid and sellers are very hesitant to realize losses, but as the Japanese market shows. Eventually they must...little by little the housing market comes off as buyers are no longer able to access the same magnitude of mortgages.

Think down 32% is bad?  Imagine you are in New Zealand where >40% of new investors mortgages and 20% of retail mortgages are interest only.  Here a 1 million dollar house here and 900k mortgage can be had for only 2250 a month...which is hard to pass up when the equivalent rent is 4000 per month or more and there are no capital gains on real estate! 

However, when rates go from 3 to 6.3% the monthly costs jump more than 100% to about 4700 a month (from 2250)! Whomever would potentially be purchasing from them or anyone like them in the market will no longer be able to. An equivalently qualified borrower will now only be able to qualify for a 430k mortgage when he could previously obtain a 900k mortgage! 

Ipso facto: home values will need to reduce by more than 50% because interest-only mortgages are very sensitive to rate hikes. Also, IR mortages have reset periods on the front end which will force the market down relatively rapidly as existing owners simply cannot afford their resets in the near future.

Western governements have not only allowed, but have incentivised massive leveraged gambling which just happened to also benefit the sitting generation of owners. 

Highly leveraged borrowers are more exposed to future increases in interest rates than others, especially as mortgage interest rates are only fixed for short periods in New Zealand - 78% of outstanding mortgages will have their interest rates reset within one year (source: OECD)

So the same generation that was forced to save to get into houses with absurd down payments on absurd valuations will now have many forced to forfeit their equity and become renters. It will take a while for many to realize that prices have stopped “always” going up.

This will include much of what is left of young men, who will have ever harder choices about how to survive such economic times.

Some simple predictions:

Each political party will try to capitalize on the stress, displacement and catastrophe 

by blaming the other side

The easy but wrong answers will win public favor 

Tensions will continue to mount

Crime will continue to rise

Political distances will continue to grow

Drum beats of war will beat ever louder

]]><![CDATA[Exorcise Omega-6s]]>https://www.revfire.us/p/exorcise-omega-6shttps://www.revfire.us/p/exorcise-omega-6sSat, 17 Sep 2022 00:18:50 GMTI was recently sent the video linked below by a good friend and reader. It speaks to what I think is one of, if not the number one health item of concern in our culture today:

 The $100 Billion Dollar Ingredient making your Food Toxic

Industrial seed oils in my opinion ruining health, taxing and emisserating the poor and increasing the likelihood our civilization collapses. If I could give everyone one rule to follow for health it would simply be:

Avoid all omega six oils - on the labels they are listed as “polyunsaturated fats”

The statement above is going deeply against the grain. If you are like I was and used to believe authoritative institutions had your best interests at heart you might think omega-6 oils are “heart healthy”.  

The American Health Association says right here that you should eat more of these oils:

AHA Recommendation:

For good health, the majority of the fats that you eat should be monounsaturated or polyunsaturated.

Foods high in polyunsaturated fat include a number of plant-based oils, including:

  • soybean oil

  • corn oil

  • sunflower oil

And here’s what the genius health bloggers at Harvard are saying (source):

“limit the saturated fats, and replace them with essential polyunsaturated fats...

Corn oil, sunflower oil, and safflower oil are common examples. Polyunsaturated fats are essential fats. That means they're required for normal body functions, but your body can't make them. So, you must get them from food. Polyunsaturated fats are used to build cell membranes and the covering of nerves. They are needed for blood clotting, muscle movement, and inflammation.”

The Harvard article is also discreetly telling the crucial truth yet summarizing as if unable to add 1 + 1. 

In the last line...what are these essential fatty acids needed for? 

A: Clotting and inflammation.  

Q: Oh, are we all sick and dying from a lack of inflammation and clotting? 

A: We are dying from excess inflammation and clotting

These experts don’t even understand their own copy. 

From my point of view these institutions should be subject to class action lawsuits similar to or worse than big tobacco. 

How can I have such a bold opinion and counter all those distinguished gentlemen and ladies and their distinguished and well padded careers?  

A: Logic, Multiple lines of logic:

  1. Common knowledge: As said above polyunsaturated fats are precursors to blood clotting and inflammation...blood clotting and inflammation are associated with every major modern disease.

  2. Countervailing science: there are more and more articles overturning the bad science of yesteryear; unfortunately, it takes a long long time for research to make an impact on doctors in practice and seats of power. 

    1. I reckon the lag to society of inconvenient facts is something like 50 years. 

      1. 25 years for dogma to be overturned in medical education and then another 25 for students to ascend into positions of authority late in their careers. 

      2. Note: Hand washing was demonstrated in 1847 to be very beneficial and it took until the late 1980s and 1990s for major government institutions to put out guidelines suggesting antiseptic soap for MDs...despite the fact that germ theory was recognized for over 100+ years prior!

  3. Chemistry: the chemistry of fat susceptibility to oxidation is known (see Wikipedia). Saturated fatty acids are less susceptible. The basic chemistry is rather straightforward and clues are in the nomenclature. “Polyunsaturated” means a molecule with many unsaturated, unsaturated by hydrogen, carbon double bonds and thus many places where oxidations are likely to occur. 

  4. Physiology: it is also known that the oxidation of polyunsaturated fats plays a significant role in the causes of aging, just as it is known that inflammation and fibrosis which are products of polyunsaturated fat reactions in warm bodies are also a drivers of aging. 

    1. Age spots - these visible markers of aging, which also occur internally, are made of lipofuscin and require the presence of polyunsaturated fat for their production.

  5. Evolution - we certainly didn’t eat any of the so-called healthy manufacturing waste product oils in the evolutionary environment while we did eat animals which were well saturated with fat and as well as plenty of plants full of antioxidant compounds - sometimes paired with monounsaturated fats. 

    1. This shifted only in the last generation. As far as I can tell ~100% of medical Mds and PhDs basically know nothing about evolution and its implications for health and disease. 

    2. Q: Should they? A: yes

    3. Q: Do they? A: no

  1. Economic correlation (probable causation). The economic data is relatively easy to find:

    This chart has a y-axis of kgs of consumed oil per person per year and an x-axis of 1949 to 1999.  

  1. Many “cultural paradoxes” really parodies fly in the face of our so-called science. Our institutions have made themselves into corrupt jokes, or rather marketing wings of ADM and Pfizer.  See “The French Paradox” for further information. 

  2. Historical origins and logic of the founding myth. The original myth was that cholesterol was the source of heart disease, lowering saturated fat lowers cholesterol production (relatively valid). Yet, the story of causality of cholesterol is refuted and yet the edifice of products, norms and propaganda it helped build still maintains.  The cause of most modern diseases is looking a lot more like inflammation and increased clotting factors...

    1. Q: Which are purportedly from?

    2. A: Essential polyunsaturated fatty acids. Ipso facto, it’s essential for you to get diabetes, hypertension and all other related modern diseases…and quick too!  

    3. As we also know:

"War is peace, freedom is slavery, and ignorance is strength." (Orwell, 1984)

  1. Economic incentives and influence - soy is one of America's biggest agricultural products...bigger than dairy or cattle.  It does not seem far-fetched to assume capture of universities, political parties and health nonprofits has occurred and is skewing so-called “science” in favor of these agricultural products despite their downstream costs to society. 

The so-called “essential” and “heart healthy” fats are exactly the opposite. Despite the clarity of the physiological evidence and its simple chemistry underpinnings, institutions of authority continue the ruse. The origin seems to simply be bad science, an error within a doctrine with positive intent, but the momentum and group think that has followed is nearly beyond comprehension, yet it is the world we are actually living in. 

It is hard to state the full impact of our errors. The massive increases in inflammation, obesity, hypertension, dementia and various other related diseases of civilization are present in our (declining) mental health, moral characters and intelligence. 

If it seems like most people around the world want overly simplified political narratives and all sides are acting hysterical. I’d suggest it’s because they do and they are. I’ve mentioned it in earlier articles, but the Flynn effect, the established though remarkable 100+ historical trend of increasing average intelligence, has been reversed for a decade...we are now, on average, growing dumber...and it shows. The near future does not look good. 

Q: How do we solve any problems when our brains are riddled with inflammation and our metabolisms are sluggish?

A: Not well, not well indeed. 

Exorcising omegas 6s: 

If you find the movie or any bits I’ve written compelling you will want to consider exorcizing these industrial waste products from your kitchen, your habits and your life. Experiment with identifying what items have the item's nutrition labels list polyunsaturated fats as significant in absolute and relative terms.  Also note that we can assume that 99% of all restaurants and restaurant items are similarly permeated with oils doing us all immediate harm. If you are as disagreeable as me simply ask any waiter or clerk what is being used when preparing your food. I do, and many of the best restaurants I used to go to have surprised me with their ingredients, unfortunately the surprises were never positive.

Even in most upscale restaurants this, or something like it is what you are getting .

and this I definitely believe is not butter:

Beef note:

Cows are some of America’s largest consumers of corn, and this happens only in their last few months of life and it’s unnaturalness in their diet drives a much higher concentration of omega-6s in their tissue - our food. Compared to most cows fed in feedlots, grass fed beef have fats with 2/3rd less omega 6 fat (source). If you are considering eating more meat in an attempt to reduce omega-6 fat exposure, keep this in mind. 

If you have not already, please make the effort to watch this video: 

The $100 Billion Dollar Ingredient making your Food Toxic

Positive note  - If you are concerned about another restriction and think what is left for me to eat.  I know it’s a mess -  the US media is demonizing sugar when they should specify that it is sugar in vehicles without the natural blood sugar regulators like potassium and apigenin...those are what we call fruit. 

Enjoy fruit 

Avoid Omega 6s 

Have many more great days 

]]><![CDATA[FundaMetals 1: Lithium]]>https://www.revfire.us/p/fundametals-1-lithiumhttps://www.revfire.us/p/fundametals-1-lithiumSun, 31 Jul 2022 19:30:12 GMT

Top Takeaways:

  1. Lithium has an interesting history

  2. Lithium in small consistent doses reduces all cause mortality including prevention or reduction of depression, cognitive decline (dementia & Alzheimer’s) & prevention of cancer metastasis among many other conditions

  3. Lithium is practical for reducing immediate socio-emotional stress

  4. Lithium is one of very few drugs or substances FDA approved outside of patent incentives

  5. Lithium Orotate is cheap - 20-30 dollars/year. The best value anti-aging substance I know of.

(transcript)

I'm gonna be talking with my dad about lithium and he can't see the screen so bear with us

we were just talking about what is lithium and I think you, and you were saying that you're aware of its use psychiatry vaguely, but, okay. It, so I have a screen up in front of me. It's the periodic table of the elements and lithium is on the far left side. And it's one of the first elements created after the big bang. So it's actually element number three. They're number they're numbered.

Hydrogen is number one. Helium is number two and lithium is number three the numbers also correspond to the number of protons in the nucleus and so hydrogen has essentially one proton and one electron and then helium has two protons and two electrons and lithium has three protons and three electrons.

And it happens to have the most common form happens to have four neutrons. But let's just ignore the neutrons for a minute. So lithium has this atomic number of three and it's on the left side of the periodic table and that's important. All of the elements on the left side, basically give away electrons very easily. And then all the furthest right on the periodic table, they actually, they either take nor gain electrons, but the ones, one, one in, from the far right.

They are very eager to grab electrons alkaline metals is what we call the ones on the far left and the ones that are eager to get electrons, they're called the halogens and when they put together they're salts and the ones you're, the one you're most familiar with are everybody's most familiar with is table salt is sodium, which is one down from lithium and it's column and chlorine, which is just over on the same with the same row as sodium.

So basically when you put salt in water, the Alka eye, the one on the far left gives away its electron it becomes positively charged and it's called cat ion and the one on the right is takes that electron and becomes negatively charged. And it's called an anion. So you put your table salt in water and it dissolves and then you get cat ion and anion in this case lithium almost always comes as a salt and it becomes in the solution it's lithium plus which means it's lost one electron there are a variety of types of salts, it's commonly found in salt form, the psychiatric, the typical psychiatric medicine is lithium carbonate lithium is, it's a metal, it's an alkaline metal and it dissolves as a salt in solution and in the body.

Maybe because you're not used to thinking about the metals that are on the far left of the periodic table, you're probably used to thinking of iron or gold. Those are all metals essentially. A huge portion of the periodic table are metals

potassium I'm is very similar. Does a lot of similar things to lithium and I'm quite interested in potassium technically it's a metal, although, it's in food, copper, zinc probably in supplements I've given you and they're they're definitely metals as well.

But we can't really, we can't really make any gross generalizations about metal. Some are terrible for you. And. like mercury is also metal and it's terrible. That's a metal terrible for you. You don't wanna, so we don't wanna make any generalizations there.

I've been spending a lot of time looking into potassium, which is chemically very closely related and and I realized I'd not done a more thorough job on lithium there have been a number of really interesting findings in lithium

it was already known to help with Mania depression it can basically prevent depression and it can treat mania. It doesn't seem to be able to treat depression once it's started, but you can be it's a prophylactic for most of the dementias, including Alzheimer's. So that's the big one.

And it seems to prevent all cause mortality. So that means from everything. So I'm trying to figure out plausible reasons why that might be the case and I think it's because it blocks certain stress hormones, and it and then by doing that, it allows more blood and oxygen and nutrients to get to essentially all the tissues and that's the main mechanism of action. Now, there are other molecules that the literature talks about at hitting, but those are secondary, in my opinion

The typical way they talk about it in the literature is not like I'm just talking about it. Although I think both are true. There's literature saying it essentially blocks adrenaline and then there's literature talking about it on the cellular level and how it inhibits this thing called GSK three.

Which basically is involved in all kinds of cellular signaling of stress. I think it's a composite thing I'm looking at the total system level and the researchers are looking at the cell just cellular only level. So I think they're both consistent, in my, the model that I'm gonna be articulating, if someone is essentially less stressed, they are increasing their metabolism.

They're perfusing their brain and their peripheral tissues with blood. They're getting better digestion and they're much more likely to live healthier and longer lives.

We already have proof of more longevity with lithium, so it's that's like a given it's just that the mechanisms are still being worked out and so I'm offering a slightly different view than the sort of a low level biochemical view, which is, I think also true.

It's just not the whole story. I'm not a medical professional, but based on the literature, it looks like it's a good idea for me and others. Human beings to ingest the appropriate amount of lithium to Live longer now what the appropriate amount probably depends on someone's potential for kidney disease and, they would, they should check with their doctor.

There are dramatically different doses for. say health effects versus pharmaceutical effects for cases of mania and bipolar. They use a thousand milligrams or more a day, or like on the order of a thousand milligrams, which is one gram.

And in the studies where they're showing longevity they're getting it from their drinking water in the order of half a gram or half, sorry, half a milligram. So there's some sweet spot that is somewhere around a milligram or maybe slightly more, less than a milligram for longevity.

And then there's a known toxic effect of, persistent use of. I'm gonna call it high doses, but high, like greater than 500 milligrams of lithium daily essentially, there's a trade off if you're getting great psychia psychiatric benefit from taking 500 milligrams or a thousand milligrams and that comes at the risk mostly of kidney failure.

Why don't I tell you I'll tell you how I'm gonna approach it for myself which is for me to try to find the minimum effective dose. So there's two things, I guess one is the risks are also related to the composition of other I'm gonna call ions and the person's diet, but especially sodium and potassium.

So you could, so the, so one is you can mitigate the risks of taking and you should mitigate the risks of taking lithium and the other is that you there's basically at a low dose, there's a negative risk of any kind of problem. So minimize the dose, ha try to find the minimum effective dose and then mitigate the risks the right amount of potassium seems to be very helpful for both like hypertension from sodium and then kidney disease from lithium.

How does a person who, know how to figure out the minimum effective dose and. I suggest that we just have to, go to the research, which is if you wanna be precautionary you take essentially only one milligram or so per day if it's only like for longevity per purposes and then then have higher doses, like five milligrams and 10 milligrams around for times of stress. Because get most likely 10 milligrams for most people is also, like not going to produce any negative physiological consequences and and it'll very effectively block a lot of adrenaline.

However what I've experienced is if you take 10 milligrams fairly consistently, you almost feel too relaxed most people will just want to reduce it to feel a little more energized

Will the effects be noticeable when I'm taking. Sufficient or even a little bit too much lithium

in my experience lithium is very obvious at the 10 and 20 milligram level.

And I think it's possible that if people are experiencing something on the spectrum of mania or bipolar, they would actually not notice that, but outside those, the potential for those conditions then they would, you should definitely notice it. People with it in their drinking water don't seem to consciously notice it, but they also don't have any experience of the opposite, cuz it's all, it's everywhere in their world, in their local world. There are studies out of Texas and Japan where it's in relatively high concentrations in the drinking water and the that's where they're showing noticeable effects on the whole population's longevity.

It's a mineral found in the dirt. It's a, it's one of the most common minerals in the universe. So it in, in rock, essentially, it's getting leached out and it's in the water with other minerals

the typical conception of lithium is as a pharmaceutical for people with with severe mental illness and. And yet it's actually all over the place. In, in some populations it's in higher concentrations in the drinking water and some it's in relatively low.

It happens to have been in the soda that became seven up. So in 1929, yeah, seven up the number seven from seven up is the molecular weight of lithium.

and up is because it prevented people from essentially made them feel better, but it doesn't actually make them up in the traditional, in the current sense of up, but it made 'em feel better. It's got this like long, this, the name that it was originally, it was called bib label, lithiated lemon lime soda.

Released it in 1929, it had lithium citrate as the primary mood altering substance. And and then it was the lithium was taken out in 1948, but that's how Sev yeah, that's how seven up got its name. And that's how it got started and it's from us mineral Springs in Georgia, the guy, whoever the entrepreneur has started bottling.

Let me see if I can pull up the guy. He started bottling the water and selling it and people.

No, he didn't add it at least initially it wasn't added as an extra, it was in the water, but he might, they might have added it later at some scale they probably had to add it, but

Coca-Cola used to have a, an active ingredient as well. Okay. What else should we, what should I make sure I cover? That's, a lot of the history I would say. The main thing I find interesting in the history is that it was a substance that didn't have a PA it doesn't really have patent protection let me just let explain this to you.

A drug has to be PA like a drug has to have a novel has to be like new, not in nature for it to be patentable. So everything that is a natural substance is for the most part UN patentable there is a giant void in our public funding, public or private funding for medicines that are from the most common elements and molecules that are around because there's no financial incentive to do the appropriate clinical trials for anything that is either a natural substance or even a pharmaceutical that is old because it's the patents of lapsed. So there's a lot of old drugs that are actually very useful for things that that will never get the right kinds of evidence to be considered part of the modern pharmacopia or pharmaceutical scheduling. I find that actually something worth potentially writing a lot more about, because I feel like there's a potential public policy solution it's bipartisan, but ultimately it's the pharmaceutical companies would not want the kind of competition from really cheap drugs.

Lithium falls into that category, but unlike almost everything else, it has proven so effective that it got a ground swell of psychiatrist writing into the FDA, asking for some kind of special authority to do a study, which then they were basically just using the lithium for that to give to their patients.

So that happened in the late sixties that Basically the FDA approved it because it was just costing them too much effort to evaluate and approve all the submissions coming in from the wave of support for lithium.

What's my conclusion? There's too many things that lithium is potentially good for. I'm reading from a Dr. Jonathan Wright, MD and some newsletter that he wrote that I found online. But anyway, all right, here are the things that he thinks low dose lithium can do:

one it's, it causes the formation of new brain cells in adults. So it helps with neurogenesis. It reduces or prevents Alzheimer's disease. It projects, brain cells against almost all toxins it increases another brain protective protein. Great. It reduces brain cell death under the experience of ischemic stroke.

It does other signaling for for brain repair it apparently it improves the sense of direction, which again, is related to the nervous system. It it'll, this is strange and takes it'll take me more looking into this, but it eliminates something called Subic dermatitis. It reduces aggressive behavior.

It reduces aggressive behavior in sorry, in both children and adults. And it reduces depression and irritability in women and aggressive behavior again in men. Let's see. And it prevents relapse for addicts to, for both drugs and alcohol. It reduces mental health burdens for hospitals. It reduces symptoms of fibromyalgia it can significantly reduce cluster headaches and it has it's been shown to be effective topically for herpes. And I think I saw one for PA virus and then it also helps fight the common cold Epstein bar and cytomegalovirus and it Treats hyperthyroidism and graves disease when combined with iodine, it can help treat gout when combined with vitamin C and I've seen, but this is, she's not on our list, but I've seen recent studies where it's helpful in fighting cancer, because it helps boost the immune system in efficient ways.

Sourcing and a reasonable strategy for use

I buy lithium orate, which is actually slightly more apparently slightly stronger per milligram than lithium carbonate, but the lithium orate is readily available on Amazon where lithium carbonate is a much harder to get pharmaceutical drug.

I buy the $7 bottle of lithium orate five milligrams and it's 120 capsules. So that's essentially four months worth of supply for somewhere around seven bucks

I think if somebody wants the benefits that I've described, that they should consider lithium I would even go further. I think it's good for relationships. And then there's, there are more conditions, I guess I'll get into later but essentially, yes. I, I would, I wanna be cheeky and say, if you want any of the benefits you should check with your conscience and, or your doctor and pursue it as you wish.

In a case of someone that is taking certain classes of blood pressure, lowering medications it's likely to make you even more drowsy or, and, or be that you would need a much smaller dose because you're retaining positive cat ions in your kidneys.

Because that's how the certain classes of drugs work. So basically the more drugs you take, the more you gotta check with your doctor to make sure that of the interactions. Unfortunately, most doctors are not gonna know. So you really just need, you can, you'll have to do the homework. You can check with me not that I'm gonna be able to give you medical advice, but can help steer people in the lines of how to do an investigation of what, what interactions there are.

Assuming someone doesn't have a kidney condition and and doesn't have a, does isn't taking any other major pharmaceuticals started there as a baseline, then it seems very plausible that taking anywhere between a half a milligram and five milligrams perpetually is like a really good idea for increasing quality and length of life.

It'll cost a grand spanking for $20 a month, a year. Sorry. yeah. 20 bucks a year it's probably the, it's probably the best bang for buck molecule right now and that's why I'm starting with it essentially is the first thing I'm talking about thanks for playing along.

Thanks for reading Metabolic Morality! Subscribe for free to receive new posts and support my work.

]]><![CDATA[Fundamentals 2: Relaxation Requires Energy (transcript)]]>https://www.revfire.us/p/relaxation-requires-energyhttps://www.revfire.us/p/relaxation-requires-energyFri, 22 Jul 2022 19:57:10 GMT

Thanks for reading Metabolic Morality! Subscribe for free to receive new posts and support my work.

Hey folks, Elliott here today. I'd like to go over another fundamental, but often counterintuitive idea in metabolic physiology and so I've titled this relaxation requires energy. The main model or the main the, an easy heuristic to. Understand what I'm talking about is to consider dead bodies, essentially dead bodies are ... their muscles within the few first few hours and days of mortality, they all contract.

And so here's a lecture at the university of Wyoming, basically talking about this phenomenon ATP is consumed at high rate by contracting muscles. The need for ATP in muscle cells is illustrated by the phenomenon of rigor mortis, which is the muscle cell rigidity that occurs in dead bodies for a short time after death.

In these muscles ATP has all been converted to ADP and the mitochondria cannot convert ADP back to ATP because there is no oxygen available. In the absence of ATP calcium transport proteins, stop pumping calcium into the sarcoplasmic reticulum and the calcium and the sarcoplasmic curiculum gradually leaks out causing the myin binding sites to be exposed on the Acton filaments of the MyFi,

the myocin proteins, grab the actin and pull once, but cannot release and pull again. The muscles therefore remain rigid in the position of death until the binding of myin or to Acton begins to break down. When you think about having a muscle cramp in your skeletal muscle, you can use the model of these dead bodies that essentially don't have enough energy.

And the reason they don't have enough energy is because It takes oxygen and glucose to turn ADP  to ATP and so without both the oxygen and the glucose they can't relax.

So this is Harvard.

I don't know, health blog, if you will. And what do they say causes cramps: exercising without properly warming up. Okay basically a lack of blood flow. So similarly, a lack of oxygen and a lack of energy molecules, which could be for muscles that can be either fatty acids, I think pytuvate or glucose.

And then a lack of the appropriate electrolytes, so magnesium or potassium and an excess of lactic acid.  Reduced blood flow to the muscles can also co cause cramps and essentially that's consistent with rigor, mortis. I just wanna make this point clear.

Let's take a quick look at

Open textbook from, British Columbia, Canada. And here's what they say is required for relaxation of skeletal muscle right here. The muscle fiber will repolarize which in some sense I is gonna be, what I would say is protein extension based on. Closing the gates in the sarcoplasmic reticulum, where the calcium was being released, essentially not allowing further calcium to be released while using then energy to drive calcium back into the sarcoplasmic reticulum.

This is the same story as rigor but just at a smaller scale, it takes energy to put the calcium in an organized manner in the sarcoplasmic reticulum here, they're just talking about what causes even fatigue the opposite of that is the use. They say it's requiring stores of ATP.

So those ATP stores get reduced during muscle function

lactic acid and the extra cellular environment in pH also affects the enzyme and protein activities of the cells and then electrolyte imbalances, are an issue and then finally, they're talking about the requirement for oxygen. Oxygen is required to restore ATP and creatine phosphate levels. And then it's also required to convert lactic acid to peruvic acid which would be and then also lactic acid into glucose, to reduce lactic acid, your cells have to use oxygen. The muscle cells have to use oxygen to rebuild their ATP. And I think I'm beating this horse to death.

Okay. So why is muscle relaxation so important?

So you have the endothelial cells.  They're the ones that are the barrier between the the whole structure and the blood flow, the blood and then you have some glycocalyx around here and  you have vascular smooth muscles around the AC the outside of that glycocalyx.

And so if you don't have enough systemic energy and you don't have enough ions, magnesium and potassium,  these muscles won't relax, which means you're going to reduce the blood flow through your vascular system. And I think that's pretty key insight for how we work.

another type of cell I wanted to talk about was the nervous cell and I think we can basically think of the brain and nervous system acting very similar to what I just described. Although the actual contractions are not contractions per se. They're they're nerve impulses. So the energy demands of the brain are primarily met by glucose, which is oxidized through glyco.

And oxidative phosphorylation. So we prefer oxidative phosphorylation to produce ATP, it's just saying it has to the brain has to have energy available to respond rapidly this paper is trying to get at the impact of the inefficient production of ATP from glucose, which is outside the mitochondria in the cytosol basically it happens when there's not enough oxygen. And so they're talking about how a deficiency of oxygen would disregulate the nerve cells and create neurodegeneration. Okay. Yeah, so we're not gonna get into that paper, but just realize that nerve the nervous system and the nerve cells require a great deal of energy and that energy has to come from glucose.

All right here is a paper of a intervention. I would say that I'm I find fascinating. GIK so that stands for glucose, insulin, and potassium. And there, there are a number of papers on the uses of GIK and this is one just talking about it in. Cardiac surgery and all I really want us to take away from this is that an injection of glucose, insulin, and potassium

significantly reduced  myocardial injury and improved hemodynamic performance in patients undergoing cardiac surgery.  And then they have a nuance with folks that have diabetes. So counter to what all of the mainstream diet folks are saying, both insulin and glucose are favorable for VA.

I'm gonna say VA dilation. They don't say it in here. We'll get to that in a second. But essentially these are factors which get energy into the cell and allow what they're calling repolarization and potassium is probably the key to when and why insulin and glucose are both vilified because they're ignoring the fact that you need the right cofactors if you will, for  efficient glucose uptake into cells. And this strange part of medicine, this niche of research, happens to know that glucose, insulin and potassium or they've provided evidence that's beneficial, at least in these cases, although they don't dig into the whole philosophy of it.

It also happens that. I was gonna say, maybe I'll have it real quickly in this, but the other paper that I've really paid attention to on, in relation to GIK is for the treatment of cancer. Researchers have essentially injected glucose, insulin, and potassium straight into can tumors, and it has essentially resolved the tumors

 Okay. So potassium and VAD dilation. I wanted to point out that the literature calls that the effect of potassium on muscular cells, hyper polarization. We talked about polarization was basically activated by ATP. So energy creates polarization and then potassium, hyper polarizes.

Anyway it essentially.  Causes vasodilation by let's go back to this

essentially, it relaxes these muscles around the edges of their vasculature through what they call hyperpolarization. I'm just gonna call that relaxation why they use that terminology. I don't really know.

And the vaso dilation. Results from again, re relaxation of a vascular smooth muscle cells subsequent to potassium stimulation by the ion. And they say it's from the sodium potassium pump. I'm not particularly a fan of the sodium potassium pump, but it doesn't really matter. It they're the models, various models work the same.

Okay. Here we go. Another paper on the role of potassium and regulating blood flow and blood pressure. So potassium is vasoactive and a direct infusion of potassium into an artery increases blood flow. And so this is basically just saying the same thing. A note for people trying to reduce blood pressure with potassium is that it takes a few weeks of increased potassium to get the full effect whereas sodium restriction can rapidly reduce blood pressure. But that's because most of the sodium is actually in the blood where in the potassium, it goes in the cells, sodium is typically kept in the blood fluid. And so when you restrict it, your kidneys will adjust with less water relatively rapidly. Okay. But I really wanted to focus on just the vaso dilation from potassium. They don't really talk about the requirement for glucose or insulin here, but let's keep that in mind. Potassium, glucose and insulin required for hyper polarization and vasodilation which is relaxation.

It happens to be the case that the pancreas requires potassium to secrete the right amount of insulin. So this is at a, at the systemic level to have insulin available, to put glucose into cells, you have to have sufficient potassium.  the pancreas.

And so deficiency of potassium means you get a deficiency of insulin they basically won't secrete enough insulin, which means  if you eat a bunch of sugar without potassium, then the sugar can't get into variety of cells

so that just goes to what the importance of potassium is in this whole consideration of energy and relaxation. Okay. So according to this paper insulin by itself has a, is also vasoactive has has it apparently stimulates insulin by itself, stimulates nitric oxide and.

Nitric oxide if I haven't made it clear already, but nitric oxide also induces vasodilation. So insulin by itself increases blood flow and that just doesn't seem to come up in any of the modern discussion of diet and insulin resistance. So increasing insulin through sufficiency of potassium, arguably is going to increase vasodilation, which is going to get oxygen to more peripheral tissues and also  allow the vascular smooth muscles as we've just seen to relax, which kind of begs the question of whether we're dealing with

elevated glucose as the problem or insulin resistance?  

Alright. Here's another paper talking about insulin mediated, vaso dilation and glucose uptake are functionally linked in humans. An infusion into an artery in the forearm causes vaso dilation, which the vasodilation seems to be augmented by simultaneous infusion of glucose. Then they speculate that the they're speculating that the  the vasodilation may depend on insulin media, glucose updates. I think we've already covered this enough times, but essentially I don't.

I don't need to speculate. Let's see if we get into any greater discussion these data support the concept of a significant functional relationship between insulins metabolic and vascular actions possibly at an endothelial level. Yeah. Okay. No kidding. All right.  that's from 1999. They just, I guess weren't with it until recently.

Okay. Insulin metabolic signaling increases, endothelial cell and nitric oxide production. We've already discussed that a little bit impaired vascular insulin sensitivity prevents that vascular relaxation. So basically if you're insulin insensitive,  you are not gonna be able to relax your VA, relax your vasculature how to get insulin sensitive, how to reduce glucose in the blood is a topic for another discussion but needless to say, insulin working effectively is actively is a good thing in the body. So we don't want to necessarily blunt insulin.

Why all the confusion about insulin? Because it's not the only thing that allows glucose uptake in cells and the reason that we think it is now is because the pharmaceutical industry was selling insulin, overselling insulin basically in order to Monopolize the diabetes market.

So here we go, insulin is important and the regulation of blood sugar, but it's importance has been exaggerated because of the diabetes slash insulin industry. Insulin itself has been found to account for only 8% of the insulin, like activity of the blood with potassium being probably the largest. There probably isn't a process in the body that doesn't potentially affect blood sugar.

So I guess what he's really saying one is that potassium is way more important for getting glucose into cells than we would otherwise think and the reason that nobody talks about potassium and muscle relaxation and glucose uptake and insulin sensitivity is because it got whitewashed  or scrubbed out of the textbooks essentially by the industry that sells insulin, cuz insulin is a highly profitable molecule. I'm not sure that's entirely true. I would say definitely potassium is highly.  important in our consideration of insulin and insulin's action on cells.

I couldn't find a paper that said insulin requires potassium for cells to uptake carbohydrates, but that seems to be the case or predominantly the case when you have, when you eat a fruit Once you're potassium sufficient and you're producing a sufficient amount of insulin.

When you eat food, which has potassium in it, you need less insulin because the potassium helps the insulin pull the glucose into the cell. We, it may be that there's only a small amount of insulin required when there's a sufficient amount of potassium in the blood. And so the question would be what is the trade off between potassium and insulin for the for pulling glucose into cells and that's it. I just wanted everyone to realize ultimately that relaxation requires energy and we can think of using the corpse, a corpse as a model for a very unre, relaxed person. A very unen energized person and the vasculature is coated in muscles and and so if you're, if you're, if you've got muscle cramps and legs or in other places, guess what, you're probably not getting enough energy to them.

And also very likely that you're not getting enough energy to your vasculature system and your micro vasculature system. And your nervous system is equally under energized and that most likely is coming from any combination of potassium deficiency, insulin insensitivity and glucose dysregulation.

So that's all I've got. And thank you for listening.

]]><![CDATA[Fundamentals 1: Bohr & Carbon Dioxide - by Elliott English (transcript)]]>https://www.revfire.us/p/fundamentals-1-bohr-and-carbon-dioxidehttps://www.revfire.us/p/fundamentals-1-bohr-and-carbon-dioxideSun, 17 Jul 2022 00:47:27 GMT

Subscribe now

Share

Hey folks, this is Elliot here, and this is my first video and a series going over some fundamental mechanisms of physiology. This is a piece I wrote on carbon dioxide and its interactions and effects on both the mind and the body and I just wanted to read this bit here, which is: the bore effect enables the body to adapt to changing conditions and makes it possible to supply extra oxygen, to tissues that need it the most. For example, when muscles are undergoing strenuous activity, they require large amounts of oxygen to conduct cellular respiration, which generates CO2. These waste products, lower the pH of the blood, which increases oxygen delivery to the active muscles.

Okay. So what is the Bohr effect?

Thanks for reading Metabolic Morality! Subscribe for free to receive new posts and support my work.

The bore effect describes the decrease in oxygen afinity of hemoglobin in the presence of low pH or high CO2.

So both the pH and CO2 have effect on hemoglobin and they basically, this says stabilized, but they hold hemoglobin in a structure that allows it to more easily depart and then enter tissues that are around it to wherever the blood is at that time. I think it's a very elegant physiological solution to delivering blood essentially where it's most needed because oxygen will be most readily released where the partial pressure of CO2 is the highest.

So if you think about breathing in oxygen and your lungs and there's a fairly high concentration of oxygen right there, and it wouldn't serve if all of it was just return off gassed. So it travels into the system at relatively low partial pressure of CO2 and goes to places which are the most metabolically active.

Also having the highest partial pressure of carbon dioxide, whether that's the muscles or the brain or the guts it's a very elegant emergent, if you will, way for the system to deliver oxygen to cells where it's needed. Okay. So here are Boar's curves on the left, we have the, what is he calling it? Oxyhemoglobin the percent of oxygen on hemoglobin and on the X axis or the bottom, we have the partial pressure of oxygen in millimeters mercury. And then we have Z axis, which is the different curves. And what it's trying to show is that at a low concentration of carbon dioxide. In this case, five millimeters mercury, you have very high affinity for oxygen on hemoglobin, even at a very low, relatively low pressure of oxygen.

And then if let's say we kept the same pressure of oxygen and we increased our CO2 to 20 millimeters of mercury, then we have. We've changed our affinity by I think more than 20, right? So this is, let's say let's call this 85 we're down here and this is 65. So we've gone 15 millimeters of carbon dioxide and we've we've changed our affinity by 20 millimeters.

on that hemoglobin by that's a percentage. Sorry. So by 20%. You can see that as your carbon dioxide percentage goes up, your affinity for oxygen goes quite a bit down. And the normal, this 40 right here is what we would think of.

A normal physiological range of carbon dioxide. Although it's probably safe to assume that in the modern society, people are moving closer and closer to 20. Okay. So why is the Bo effect important if I haven't made it clear yet it's important because the bore effect makes clear the importance of carbon dioxide for the delivery of oxygen to tissues.

And so it's not simply breathing more that gets us more oxygen. We actually need to consider a range of other factors for how our cells are gonna get the oxygen they need. All right. So beyond the Bo effect, we have. The fact that the ratios of oxygen and carbon dioxide also affect the release of nitric oxide and that in turn affects the vaso dilation or constriction of the same blood vessels.

So when you have more carbon dioxide, the tissues release more nitric oxide and they vaso dilate. So let's just point that out here in this study carbon dioxide influence from let's see what year 2011 carbon dioxide influence on nitric oxide, production and endo endothelial cells. And astrocytes so the thing I wanna just point out here is that. nitric oxide production is increased during hyper. This is increased carbon dioxide, and then nitric oxide is decreased during hypopnea this is reduced carbon dioxide, regardless of pH. So increased carbon dioxide increased NO increased vaso dilation, increased blood flow.

So you. you have extra carbon dioxide, you get more blood flow from bigger tubes, bigger pipes in the vasculature, and you get easier oxygen disassociation for hemoglobin. And that's just all part of this elegant system for delivering oxygen where it's needed.

And how is carbon dioxide a s ignal of where oxygen needs to go? Essentially carbon dioxide is the output of oxidative metabolism.

The basic not to get into the CREB cycle, but the basic, condensed formula is something we could all know, which is you breathe O2 and you, your body makes or eats. And then eats food and then makes glucose mostly. And those two together become water H two O and carbon dioxide.

Anywhere there's meta metabolic activity, from oxidative metabolism, you're getting CO2. If the cells are using their energy, Through some kind of activity, then they are putting off CO2, which is causing local vaso dilation and recruiting oxygen to the scene. All right. So we looked at those curves but we can look at this paper the title of this is hyperventilation syndrome, a diagnosis begging for recognition and this is an argument which has been entirely ignored by psychiatry in the pharmaceuticalindustry because it would not serve their purposes, but essentially the authors are trying to make the argument.

when you hyperventilate and you off gas CO2, and that is basically the main cause for all kinds of psychic distress. What I wanted to really take from this was the massive change in blood flow delivery from a relatively small change in partial pressure of carbon dioxide. So if carbon dioxide is retained a little bit, so each millimeter of mercury, which is really just a way of describing the concentration then there's a 2% increase in cerebral blood flow and what we, so then what we need to know is, how much does how much does. the CO2 change for certain different states for breathing fast in a hyperventilation hyperventilatory state. How much will our blood flow change?

I found this paper trying describing that they're doing it with a ventilator.

Acute hyperventilation increases the central venous to arterial partial pressure of carbon diox. Difference in stable septic shock patients. So what they've done is they've put these patients on ventilators and they're monitoring their change in concentration of carbon dioxide. So they went from starting points of an average of 44.5 to an average of 34 over the population.

So we're looking at about 11, 11 and a half millimeters of mercury. So in these folks, they would if that 2% holds, they would've, lost something 22 to 23% of their cerebral B blood flow, would've been constricted away. And that doesn't even, so that's a smaller number than the actual amount of oxygen delivery.

So they're losing 20 per 2% of the volume, and then they're losing an even greater. at least in this paper and I haven't done the math, but they're losing a, like whole other amount of oxygen delivery from the change from this change of the affinity of the hemoglobin. So they lose 22% and then let's say what is a difference of 10?

Get us? I don't know what their oxygen pressure would be. So we would have to figure that out, but let's assume that they we gonna be over here. I don't know. So we can't really say, have to do more work to figure out what the percentage loss of oxygen delivery would be based on the difference in both volume and volume of blood.

And. Change in affinity, but anyway, need needless to say, it's going to be greater than 23%. So you could lose, 20 to 40% of your blood flow or your oxygen delivery to your brain just by hyperventilating a little bit a side note, a relevant note is that this kind of thing, this change of Oxygen delivery.

You can induce panic from hyperventilation and I thought it was also curious that you can infuse lactate, which is the byproduct of non oxidative metabolism. So both of these are so basically this is a lower a lower pH plus a signal of very inefficient metabolism and that induces panic, okay. And then here's another paper describing what a relatively normal, oh, this is saying. They're using that lactic acid test to induce panic.

And they're finding out that if you actually have a normal percent CO2 in your blood, then you're actually relatively immune to that panic. How I into that panic. However, if you have a lower than 40 per concentration, then your. Susceptible. It's just something that is consistent with the same story, and here is Patrick McEwen who teed up that one of these studies, but also is a built a whole brand around slow, shallow breathing to reduce the oxygen concentration increase. Carbon dioxide concentration and allow more oxygen delivery to the cells. And so I wanted to just capture him talking about this change in peripheral blood and oxygen delivery.

Magarian in the 1984 in a paper called hyperventilation and diagnosis, begging for recognition said that every one millimeter drop of CO2 reduces blood flow to the brain. By 2%, we also know from other papers that 30 seconds of hard breathing can lower arterial CO2 from normal of 40 millimeter of mercury pressure down to 20.

Well, if there's a 20 millimeter drop of arterial CO2, it translates into a 40% reduction of blood flow to the brain and that's as a result of 30 seconds of hard breathing

all right.

He's trying to make the point that you can lose even more than what I was suggesting in blood volume. So that's only 30 seconds of hyperventilation. And I guess if you were anybody, has experienced panic attacks they don't just last 30 seconds. So we're probably off gassing, even more carbon dioxide, probably down.

Sub 2010 millimeters of mercury range. I wanted to finish this up with some other uh, factors that can come into play adrenaline when it's relief evokes a higher sensitivity to carbon dioxide. So one, one thing I haven't mentioned yet. We naturally breathe to our set chemo receptors for carbon dioxide. So one, we will breathe faster to the extent that we are more sensitive to carbon dioxide or to the pH in our blood and hormones like stress hormones Will change that receptor sensitivity.

I don't have a full list of those things that will increase our sensitivity, but it's something for me to dive into, but you can just use your intuition that essentially if you're mind is producing adrenaline or cortisol and it will intelligently make your body. Increase the sensitivity so that you breathe more and that is in preparation for some kind of physical, or I guess cognitively challenging event.

But if that physical event doesn't occur, then you've just put yourself in a hyperventilated, state. and you're gonna feel very anxious. So what we think of as psychiatric problems are deeply related to metabolism. And before I finish this relatively quick video, I just wanted to say that I found this little tidbit interesting.

As I've been messing around with the alkaline metals and looking deeply into those we just saw that adrenaline increases sensitivity to carbon dioxide and turns out that lithium blocks adrenaline. It's giving a bit of the story for how lithium works in bipolar disorder. And it's doing that by reducing epinephrine, which is adrenaline. If you wanted to reduce your own sensitivity to carbon dioxide and breathe more shallowly you could just take lithium and that's all I've got for you. Thank you very much.

Thanks for reading Metabolic Morality! Subscribe for free to receive new posts and support my work.

]]><![CDATA[A Financial Tangent]]>https://www.revfire.us/p/a-financial-tangenthttps://www.revfire.us/p/a-financial-tangentWed, 22 Jun 2022 22:49:39 GMTGiven that delayed future pain I’ve been waiting even hoping for is finally arriving in the markets and economy I thought some of my friends and family might like to know to whom I look to for related news and analysis. My only claim to credibility is that I studied economics and worked in finance just long enough to come to terms with the absolute charade that flows from how government and academia believe markets work.  

We live in a world rife with autocoprophagia.

YUM!

In my experience driven opinion, mainstream financial news is designed to drive investment activity, political ideology and confer status onto people who’ve studied the pseudoscience called economics at a few institutions of power, not as might be expected, to inform or educate. All the thinkers I look to in this space make efforts to incorporate banking, money and debt (which neoclassical economics ignores) and they do not believe in equilibrium which most powerfully enables mathematically based hypnotic trances on the public and civil service. After all, a little psychological equilibrium would be nice wouldn't it.

That said, there are some people actually trying to simply articulate and educate a wider audience on a model or models much closer to the world we actually live in. Here is my short list:

How The Economic Machine Works by Ray Dalio - Ray Dalio in my opinion is the best mixture of clear and accurate. Financially, he’s a made man who seems to be trying to give back before he leaves this world.  The above is a great 30 min overview of how the financial world really works.

His recent analysis on the Fed and costs we will bear.

Stoic Finance - This news with clear and relatively more accurate explanations. The link is to a recent discussion of how US housing will fall over. 

Epsilon Theory - These guys are brilliant (an advanced read generally) but they talk about all the technical, social and political underpinnings of all things finance.  They emphasize the psychologically emergent meme spreading nature of investing trends.

A recent relevant excerpt that is the core of all current chaos:

So long as the academic Fed continues to use a set of essentially linear, monotonic models to understand the relationship between the price of money and real world economic behaviors, their predictions will be just as wrong in the hiking stage of ZIRP monetary policy as they were in the cutting stage.

The Fed will overestimate the impact of rate hikes on curtailing inflation in exactly the same way they overestimated the impact of rate cuts on stimulating inflation.

Will hiking rates off the near-zero line make a difference in economic behaviors? Oh yes! Just not the behaviors that the Fed (and the White House) expect.

Cutting rates from 4% to 0% did not spur real world inflationary behaviors, it spurred market world financialization behaviors.

What is financialization?

Financialization is profit margin growth without labor productivity growth.

That sounds like a small thing, but I tell you it is EVERYTHING.

Financialization is the smiley-face perversion of Smith’s invisible hand and Schumpeter’s creative destruction, where profit margin growth is both pulled forward from future real growth and pulled away from current economic risk-taking.

Financialization is tax and balance sheet arbitrage to leverage laws passed by bought-and-paid-for politicians.

Financialization is stock buybacks to sterilize stock-based comp awarded to entrenched management.

Financialization is the acquisition and burying of smaller competitors to create an insurmountable, anti-competitive moat of scale in every economic sector.

Financialization is the zombiefication of an economy and the oligarchification of a society.

What has the last decade-plus of Fed interest rate cuts and balance sheet expansion given us? Not stable prices with healthy 2% inflation expectations. LOL.

No, the last decade-plus of Fed monetary policy has given us this, the worst stretch of labor productivity growth in the history of the United States of America, not coincidentally occurring alongside the greatest stretch of financial asset appreciation in the history of the United States of America.

[mic drop, exit stage left. RUN!]

If you want to dig even deeper I recommend the books below - all are focused on debt:

Ray Dalio (Big Debt Crisis)

Steve Keen - The Only Economist Incorporating Debt-Money and Using a Nonlinear Systems Dynamic Model to Investigate Economic Relationships

David Graeber (5000 Years of Debt) - His research ends standard stories about the foundations of economic activity. Hint: the foundations are social relationships involving debt not so much barter. Debt is actually much more sophisticated than barter and exchange and has deep roots in moral behavior and psychology.

This Time Is Different: Eight Centuries of Financial Folly - Title Speaks for Itself

]]><![CDATA[Cancer & Metabolism ]]>https://www.revfire.us/p/cancer-and-metabolism-primerhttps://www.revfire.us/p/cancer-and-metabolism-primerFri, 03 Jun 2022 01:50:54 GMTAnd so castles made of sand

melt into the sea eventually  

Jimi Hendrix

There's something wrong with the world today

I don't know what it is

Something's wrong with our eyes

We're seeing things in a different way

And God knows it ain't his

It sure ain't no surprise, yeah  

Aerosmith

Intro

Fear of cancer is evermore common and perhaps rightly so. In western society today you have about a 1 in 2 chance of having cancer in your life if you are a woman and about 1 in 3 chance if you are a man. It's the second leading killer after a cardiac event. It has touched all of our lives and will continue to do so for the foreseeable future.

In this light, I've drafted this cancer focused metabolism biased literature review and update. I hope you will find the below both efficacious and compelling enough to drive agency and hope. While what I'm writing about is focused on cancer, many concepts, substances or modalities suggested are often worth considering for overall health. In my physiological worldview all diseases are deeply systemically related.

Caveat about my credibility and sanity

I’ve written something below that will make me sound like a loon and maybe socially detestable and yet I am stuck with a brain trying to make the most sense of the corpus of information I've looked into. The more I look into any given condition the more I find myself uncomfortably at odds by what is considered established knowledge. I know that I am a bit of a contrarian but perhaps that results from simply wanting to know what really works and caring a good bit less about what other people think. I might be completely deluded by my own ignorance. I do search for deep simplifications in a world of nuance and potential chaos. Maybe the answers I tell myself are completely invalid. That said, what has even to me seemed crazy at first seems now to add up from multiple independent perspectives.

To check myself for mania or grandiosity, I'm not inventing anything, I'm simply reading widely and then writing on and amplifying perspectives that, to me, seem to make the most sense. It turns out that in so many cases including cancer below, only a modicum of effort seems to overturn common knowledge and practice. As uncomfortable as it may be, I am forced to accept that the fundamentals of medicine and biology have been so corrupted by prestige politics, dogma and economic priorities that those inside this kind of cult can’t fathom that they might be looking exclusively under lights all pointing in the wrong direction.

The Environment of the Old Paradigm

Without being too cynical we should ask ourselves how this might actually be possible. It seems to me that without any explicit corruption we can see that funding sufficient for FDA approval can only, economically, be granted for patent-able molecules. This constraint on investigation and research dramatically limits the types of treatments that can be under proper investigation for future clinical use. The excluded world of molecules includes substances produced by nature, and previously patented or old drugs and common substances.

While there is a significant body of primary research consistent with a metabolic view of cancer, and molecules and interventions on hand, who would put forward the money? We have no public entity or institution for this, and private entities cannot be expected to invest millions or billions to put effort into demonstrating the efficacy of an unpatentable molecule. Doing so offers little to no financial benefit and could make their whole portfolio of drugs worthless. All of that is rationalization for holding a view wildly outside of popularly accepted models.

The Metabolic View

The standard view of cancer relies upon the genetic mutation hypothesis as a key assumption. The whole of the profession takes this very fundamental assumptions for granted. Most of the field would probably not consider a metabolic explanation even an option for investigation. Yet, the metabolic explanation is relatively consistent with evolutionary development and places the origin of cancer with local environmental factors working through the cell’s metabolism. This is not to say there is no place for genetics. Individuals with certain alleles will certainly be more likely to get one or another type of cancer, but I would like to suggest that for most types of cancer the largest contributing factor is the micro-environment of cells and tissues. That environment, the cancer environment, has identifiable characteristics which we can identify, understand and use to avoid or resolve cancer.

Warburg

The metabolic explanation for cancer has roots with Otto Warburg who was in his time awarded a Nobel prize for his work on cellular physiology. The Warburg hypothesis was postulated in 1924 after the metabolic work that won him the Nobel. He found that cancer cells primarily undergo glycolytic metabolism instead of oxidative phosphorylation and he believed that faulty metabolism was the cause and not the result of cancer. Warburg thought that cancer cells' mitochondria were dysfunctional and those dysfunctions lead to fermentation.

“Cancer, malignant growth, and tumor growth are caused by the fact that tumor cells mainly generate energy by non-oxidative breakdown of glucose (a process called glycolysis)."

"The prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar."

This is in contrast to healthy cells which mainly generate energy from an oxidative metabolism. Somatic mutations will be present, but the occurrence of lactate, inflammation and other tumor microenvironmental factors is prerequisite. This is an old idea recently returning to fashion. I am only surfing the current wave of interest and literature looking in the same direction. Interest in the Warburg Effect and the metabolic theory of cancer is rapidly growing. Hopefully with all the renewed interest we will find some new types of patentable cancer combating molecules and bring much more money into alignment with how cancer seems to really work.

Evo-Devo Primer

All cells in a body, excluding the gametes, have the same DNA and they all have to figure out what they are to do. Making proteins from RNA and ultimately from DNA is dependent on environmental conditions. There is a whole field of biology working out how specific signals from the environment influence what cells mature into and ultimately how an organism gets its structure. This is evolutionary developmental biology or "Evo-Devo." This field is keenly aware that genes themselves are regulated by their cells. Without going into any specifics we can outline the problem of a cell figuring out what it should express phenotypically. That is, a kidney cell has to figure out it’s to express a kidney cell program. Among a number of factors like light, temperature, forces of strain, the availability of oxygen to a cell and its neighbors is a critical input for the cell determining where it is, what it is and what it does. Of course, this involves genes but the causality begins in the environment of the individual cell. The origin is structural, environmental. Genes do not decide what to do, including mutating (or not reversing existing mutations) without specific inputs from their local environment.

Chemical Respiration

An understanding of basic cellular respiration and metabolism will help us better grasp the metabolic perspective. The typical energy producing mechanism of respiration is known as oxidative phosphorylation. Here is a input output representation of cellular oxidative phosphorylation:

An alternative metabolic process, used when something impedes oxidative phosphorylation is fermentation. In fermentation glucose, adenosine diphosphate (ADP) and phosphate (P) become lactate and adenosine triphosphate:

Oxidative Phosphorylation:

Glucose ( C₆H₁₂O₆) + Oxygen (O₂) + ADP + P =>

Carbon Dioxide (CO₂) + Water (H₂O) + 2 ATP

Glycolysis/Fermentation:

Glucose + ADP + P => Lactate + 38 ATP

You don't really need to know what any of the molecules look like, but what is really critical here is that in fermentation cells only get 2 ATP for every glucose while they get 38 ATP from oxidative phosphorylation. For oxidative respiration the cell requires oxygen and all the factors that facilitate the TCA or Krebs cycle. Fermentation produces lactate and CO2 while respiration (oxidative phosphorylation) produces H2O and CO2. Fermentation takes place in the cytosol respiration takes place in the mitochondria.

Metabolic by-products are not inert.

The main product of glycolysis, lactate, is inflammatory and a primary driver of angiogenesis. Lactate production can be self-reinforcing when low energy and inflammation persist. Angiogenesis is the production of new blood vessels, which can be seen as a cell's attempt to demand or request more blood and to then revert to oxidative phosphorylation. It is also a hallmark of cancer and other metabolic stress related conditions such as macular degeneration (A Metabolic Look at AMD). This is why angiogenesis inhibitors are often used in an effort to prevent tumor growth and metastasis.

Despite the association with cancer, angiogenesis is appropriately required for routine repair of the body. Muscle physiology and adaptation offers a relatively straightforward example of the beneficial effects of angiogenesis. When muscle is used without sufficient oxygen delivery from the blood, lactate is produced through glycolytic fermentation. That lactate which we feel as a burn with its associated inflammation recruits local reconfiguration such that more oxygen from blood flow will be available upon recovery. This is a significant part of adaptation to exercise. Some tissues, such as muscles seem predisposed for an ability to adapt without structural pathology, while other organs like the eyes and retina are not. As described previously, the retina is one of the most metabolically active cells in the body and without sufficient glucose or with too much inflammation it will lose its critical structure as it reconfigures to maintain its metabolism.

Cancer and Developmental Regression

Another appropriate place for lactate and angiogenesis is for the survival and development of the cells within an embryo which has adhered to the wall of the uterus. The embryo produces lactic acid which:

1. Compels local tissue dis-aggregation

2. Elicits Vascular Endothelial Growth Factor (VEGF) (which promotes angiogenesis)

3. Modulates the immune system - turning it down to reduce chances of being rejected by the host. These features are all required for the embryo’s survival and as the angiogenesis brings more blood with oxygen the blastocyst’s cells turn to respiration which then signals greater differentiation.

All the three behaviors above are also hallmarks of cancer.

The Unsung Hero

Believe it or not, CO2 is not a pollutant. CO2 is anti-inflammatory, a trigger of vasodilation with increased blood flow and the reactant that combines with ammonia to make urea. Ammonia, in the absence of CO2, is known to pool in the tumor microenvironment to stimulate further cancer growth. As we might remember from this series, CO2 increases the local availability of oxygen through the Bohr effect (Mind, Body & Carbon Dioxide) and CO2 feeds forward its own production facilitating more local respiration.

Cells finding themselves in environments of high lactate, high inflammation, low oxygen and/or limited inputs to oxidative phosphorylation become cancerous. In this light, increasing CO2 from oxidative phosphorylation is a reasonable approach to preventing or treating cancers. And luckily for this argument there already exists a whole line of research in Korea applying just such an approach on many different types of cancer:

“We previously found that trans-cutaneous application of CO2 with a hydrogel decreased the tumor volume of several types of tumors and induced apoptosis via the mitochondrial pathway.”

For those still clinging to a mutagenic origin of cancer, studies in other domains have further dismantled the fundamental logic:

It has been shown that cancerous nuclei transplanted into normal cells with normal cytoplasm differentiate into healthy cells, while healthy cell nuclei transplanted into cancer cells remain cancerous. From related research full organisms have also been growing from cells where the nucleus were once cancerous. It is also the case that early cancer cells typically do not have genetic mutations, mutations increase with tumor progression. None of those should be possible if genetic mutations are the origin of cancer.

Cancer in historical context

Cancer rates historically and prehistorically were much lower than today and our closest primate cousins have dramatically lower rates of cancer. Rates in our species have risen much faster than genetic transmission can account for, and incidence is correlated with other modern lifestyle diseases like hypertension and diabetes.

Evolutionary and stress biology have shown that stress is the causal factor for mutations including those seen in cancer. This is conveyed best by the work of Denis Noble who extended the work of Barbara Mclintock. This is the important alternative hypothesis to why cancer cells often have so many mutations. Cells respond to stress with both modified respiration and genetic rearrangement. The more stress the more mutations one would expect to see. The metabolic approach shines light on why we haven’t “solved” cancer in five decades supposedly dedicated to fighting.

Thomas Sigfried, is a modern champion of the view that cancer is a metabolic disease, but he is unfortunately also fairly focused on sugar being the culprit. Cells in glycolysis consume enormous amounts of glucose. So he and others in his camp assume excess sugar is to blame and the remedy they seek in this view is to use blood sugar lowering medication that reduce glucose so low that the cancer is starved and dies. Given his case studies of success I only argue that there are seemingly easier ways to approach the same problem. Foremost is to ensure oxygenation of the area and paradoxically that means more CO2. Other Krebs cycle and mitochondrial factors also need to be attended to and some experimental evidence supports a view that enlisting glucose rather than lowering it directly interrupts the cancer process. Specifically, delivering thyroid, sugar, insulin, and potassium directly into a tumor has been shown to cause tumor regression. “We conclude that TGIK [Thyroid, Insulin, Glucose & Potassium] has anti-tumor activity when administered intratumorally”. Based on my pubmed searches little further effort has been made to determine the optimal ratios or dose, but the approach seems very promising for patients, though not so promising for the cancer industry.

It seems to me plausible, even probable that cancer is mostly a disease of the tissue microenvironment predominantly associated with local glycolysis, lactic acid, hypoxia, inflammation and local and bodily stress. Inflammation is what connects cancer originating in the lung from particulate irritation to a cancer initiated by tissue fighting a virus, bacteria, or fungus. When inflammation is high and the local tissue is hypo-metabolic, the ground for tumor emergence is set. It is also worth noting that nutrient deficiencies preventing oxidative phosphorylation will increase the odds of cancer.

A few supporting videos with structural metabolic views of the origins of cancer:

Mina Bissell: Experiments that point to a new understanding of cancer | TED (16 mins)

Thomas Seyfried: Cancer: A Metabolic Disease With Metabolic Solutions (~1 hour)

Getting practical:

Cancer prevention and reversal, what might we utilize outside of standard medical practice:

  1. Increase CO2 in our blood and cells

    1. Exogenous: Carbogen

    2. Endogenous: Promote oxidative phosphorylation

  2. Block lactic acid production --> inhibit carbonic anhydrase 

  3. Increase bicarbonate

  4. Melatonin

  5. Stabilize cell structure to reduce cell division:  increase potassium & progesterone

    1. Recall progesterone will increase thyroid and temperature

  6. Use heat to Increase metabolism, blood tissue perfusion and tissue oxygenation

  7. Reduce inflammation: Increase Vit D, Aspirin, Melatonin etc. Various

  8. Prevent Metastasis with Lithium

  9. Increase metabolism from oxidative phosphorylation

  10. Block cortisol (Progesterone, Pregnenolone, DHEA) eat sufficient sugar from plants full of potassium

  11. Inhibit fatty acid oxidation (FAO)

  12. Aromatase inhibition

  13. Pro-oxidant Vitamin C

  14. Hydrogen Gas

  15. Hyperbaric Oxygen Therapy (HBOT)

More details: 

  1. Increase CO2 in our blood and cells 

    1. Exogenously:

      1. Get a Carbogen and a cannula

        1. https://www.consciousbreathing.com/carbohaler/#

      2. Pump pure CO2 into a bodysuit or bag

        1. https://www.consciousbreathing.com/product/bodystream/

      3. Buy Co2 canisters and fill up bags or a dry suit

    2. Endogenously

      1. Eat for a higher metabolism:

        1. More sugar esp from fruit

        2. More calories from nutrient dense food

        3. Eat meat & vegetables that are well cooked

        4. Take HCl and enzymes if needed

        5. Manage thyroid for mild hyperthyroid based on temperatures

      2. Reduce all anti-metabolic substances

        1. Polyunsaturated fats 

        2. Anything that irritates the gut (person specific)

        3. Avoid gums esp carrageenan

        4. Avoid highly processed foods

        5. Avoid gluten (precautionarily)

        6. Reduce Iron

        7. Reduce Methionine

    3. Move to a place like Colorado (less oxygen pressure) -

      1. Colorado is one of the only states in the US with an obesity rate < 25%

  2. Block lactic acid formation, inhibit carbonic anhydrase

    1. High dose Thiamine (500mgs+) daily

    2. Spermidine

    3. Acetazolamide 

    4. Combine with bicarbonate for best results

      1. Common side effects of paresthesias, dyspepsia, lassitude and fatigue in 30 - 40% of patients are generally tolerable or abate, but if not can be partially relieved by bicarbonate supplementation. 

      2. https://www.researchgate.net/publication/260680185_Safety_of_carbonic_anhydrase_inhibitors

  3. Significantly increase bicarbonate for periods at a time

    1. Ingest potassium bicarbonate

    2. Some people use sodium bicarbonate but I suggest potassium bicarbonate only

  4. Melatonin is massively anticancer

    1. One known pathway is by promoting oxidative phosphorylation and preventing Lactic acid, however more mechanisms are being worked out

    2. Melatonin is also high anti-estrogenic and promotes immune function

    3. Melatonin happens to be the bodies strongest antioxidant 

  5. Progesterone and potassium

    1. Progesterone 

      1. One of Progesterones main metabolites is a strong aromatase inhibitor for (ER alpha+ breast cancer, prostate cancer)

        1. For men DHT and androstenone are probably better

      2. Progesterone (real progesterone) prevents or reverses Estrogen induced cancers (progestins do not)

    2. Potassium (I think this could be much more important but it’s only being explored recently)

      1. Potassium is essential to proper cellular structure and function, energy storage and metabolism - modern diets are woefully deficient 

      2. One of progesterone’s mechanisms of action is to increase reabsorption of potassium and excretion of salt while reducing extracellular potassium probably be means of increasing oxidative phosphorylation and thus energy capture & utilization

      3. Green drink, juicing and vegan approaches to cancer remediation including Gershon diet for reducing cancer actually have merit and Potassium surplus is their main mechanism (Along with natural aromatase inhibition):

        1. Systemically increased Potassium and reduced sodium 

      4. Potassium is antihypertensive, and fibrotic, and is now being show to mitigate cancers and support immunotherapy

      5. The cost and risk of increasing potassium upto about 11 grams/day are quite low. I would aim to double the daily RDI of potassium ( I will write more on potassium benefits and basic lack of risks in the near future)

        1. Potassium is being used to treat Rheumatoid Arthritis (alone)

        2. Already used to treat Hypertension 

        3. And is likely remediative in diabetes

  6. Use heat and light (maybe a virus or two)

    1. Hyperthermia to Treat Cancer - NCI

      1. NCI believes in it, they just don’t want you doing it yourself

      2. Raise internal heat through metabolism

    2. Get phenomenal, but safe loads of sunlight on your skin

      1. Maximize natural vitamin D production

        1. Does sunlight protect us from cancer?

        2. Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort

      2. Stop taking cholesterol lowering drugs (they don’t reduce all causes of mortality - guess why?) 

        1. Exposure to statins and risk of common cancers: a series of nested case-control studies - Outcome studies show lower CVD risk for people with high risk, but this is the tradeoff for lowering cholesterol rather than lowering cardiovascular inflammation

    3. Consider mistletoe for a fever

      1. Fever Therapy With Intravenously Applied Mistletoe Extracts for Cancer Patients: A Retrospective Study - PMC

      2. https://journals.sagepub.com/doi/pdf/10.7453/gahmj.2012.1.1.006

    4. Consider a flu for a fever

      1. Immunity over inability: The spontaneous regression of cancer 

    5. Coley’s Toxins are the roots of modern immunotherapy

      1. Modern immunotherapy  should be investigated and used if:

        1. Allowed, funded, available etc.

      2. Some strong immune modulating substances are:

        1. Vitamin D

        2. Melatonin

        3. Astragalus

  7. Reduce Inflammation

    1. Reducing Inflammation should definitely be part of the effort to prevent or treat cancer, but most antiinflammatories will have other features and be listed elsewhere in this discussion

    2. My top list:

      1. Aspirin - has been shown to improve cancer outcomes in many studies, but is being contented (I think the incentives are more economic than based in science) 

        1. Is a potent potassium excretion inhibitor

        2. Is a carbonic anhydrase inhibitor

        3. Increases endogenous temperature/metabolism

        4. Useful doses for cancer are likely much higher than for a minor ailment

        5. Inhibits COX-2, important to cancer development

      2. Vitamin D

        1. The liver takes  7+ days to transform to active form but I would usee 20-30k/day with vitamin K ius if cancer was an issue.

        2. Among many pathways Vitamin D - opposes fibrosis

      3. Astaxanthin is anticancer, we are still uncovering how/why

      4. Melatonin - already mentioned

  8. Prevent Metastasis with Lithium

    1. “lithium was found to prevent metastasis to the lungs, liver and lymph nodes by inhibiting TGFBIp-induced tumor lymphangiogenesis.” Increase metabolism from oxidative phosphorylation

  9. Increase Endogenous Metabolism

    1. Everything above should help - using thyroid (triiodothyronine, T3) exogenously would be a good idea IMO esp with a cancer diagnosis, but even simply with aging and exposure to modern life

    2. Co2 increases it own production in a feed forward cycle

    3. Progesterone increases thyroid

    4. We should increase and not fear sugar especially from sources with high potassium

    5. We should avoid antimetabolic agents

      1. Polyunsaturated fats

      2. Xenoestrogens

      3. Anything that irritates the gut

      4. Heavy metals in large fish and other vectors

  10. Blocking/reducing stress hormones and haemodynamics is important to being able to fight cancer

    1. Stress physiology is a precondition to cancer physiology because it signifies energy expenditure exceeding availability which means:

      1. Lactic acid production

      2. Angiogenesis

      3. Immune suppression 

    2. Glucocorticoids suppress cancer cell apoptosis

    3. Dopamine inhibits angiogenesis

    4. Personality expressions with less dopamine, (thus more serotonin) are considered to have a cancer phenotype by Psychiatrist Gabor Mate

      1. When the Body Says No - Dr. Gabor Maté

  11. Contrary to fans of ketosis, cancer seems to be able to metabolize even thrive on fat, while substances like Niacinamide which opposes Fatty Acid Oxidation seem to help reverse or eliminate cancer:

    1. “Many recent studies have provided significant evidence to support a "lipolytic phenotype" of cancer. FAO, like other well-defined metabolic pathways involved in cancer, is dysregulated in diverse human malignancies. Cancer cells rely on FAO for proliferation, survival, stemness, drug resistance, and metastatic progression.“

  12. Aromatase inhibitors (AIs) - Aromatase is an enzyme that converts androgens to estrogens.  Estrogens stimulate non-oxidative metabolism and cell replication. Aromatase inhibition is already a known adjuvant to cancer treatments specifically Estrogen Receptor + cancers, but I would suggest not widely enough. The idea that prostate cancer is from testosterone has been debunked, but aromatization should be much more highly attended to and used therapeutically. Risks of bone loss can be mitigated with high dose vitamin D and K2. Note the source of chemical AIs are mostly from steroids built off of androstenedione and flavonoids:

    1. Citrus peel

    2. Androgens like adrostonede and DHT

    3. Extremestane

  13. Pro-oxidant Vitamin C

    1. Looks like someone in the US government is up on the use of supraphysiologic doses of Vitamin-C (

https://www.cancer.gov/

    1. )

    2. Good luck getting it from your doctor, but you can simply setup a DIY project by watching a few videos

      1. Maybe it can be done orally with liposomes: Homemade megadose vitamin C (Grandfather University with Dr Peter Couttie)

    3. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues 

  2. Hydrogen Gas:

    1. Hydrogen gas (sounds crazy I know) but seems to check out as a very low risk adjunct to treating essentially all diseases including cancer.

    2. “H2 has significant anti-tumor effects”

    3. “Growing evidence has shown that hydrogen gas can either alleviate the side effects caused by conventional chemotherapeutics, or suppress the growth of cancer cells and xenograft tumor, suggesting its broad potent application in clinical therapy”

  3. Hyperbaric Oxygen Therapy (HBOT)

    1. Hyperbaric Oxygen Therapy is useful for cancer because it simply increases oxygen delivery to tumor cells as more oxygen is carried in plasma under pressure

    2. “HBOT not only improved tumor hypoxia but also suppressed tumor growth” 

    3. I’m personally less excited about more oxygen this way (given its current costs), but think it could synergize well with CO2 therapy

References:

Metabolism/Warburg

Ammonia stimulates breast cancer growth and proliferation A.... | Download Scientific Diagram

The Warburg Effect: How Does it Benefit Cancer Cells? - 

Lactate modulation of immune responses 

Difference Between Fermentation and Respiration | Characteristics, Process, Comparison

Frontiers | Role of Lactate in Inflammatory Processes: Friend or Foe | Immunology

Lactate production by the mammalian blastocyst: Manipulating the microenvironment for uterine implantation and invasion? - PMC

The Warburg Effect in Cancer

Thomas N. Seyfried, Cancer as a Metabolic Disease: On the Origin, Management and Prevention of Cancer (Hoboken, NJ: John Wiley and Sons, 2012): 195–206.

Sex Lies & Menopause (citing several others)

 “For over six decades reductionist approaches to cancer chemotherapies including recent immunotherapy for solid tumors produced outcome failure-rates of 90% (±5) according to governmental agencies and industry.” Analyses of repeated failures in cancer therapy for solid tumors: poor tumor-selective drug delivery, low therapeutic efficacy and unsustainable costs

CO2

Optimization of antitumor treatment conditions for transcutaneous CO2 application:

The effect of transcutaneous application of carbon dioxide (CO₂) on skeletal muscle

Does Baking Soda Function as a Magic Bullet for Patients With Cancer? A Mini Review - PMC

Carbon dioxide inhibits UVB-induced inflammatory response by activating the proton-sensing receptor, GPR65, in human keratinocytes | Scientific Reports

The effects of CO2 on cytokine concentrations in endotoxin-stimulated human whole blood

Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors

A potentially good side of carbon dioxide

ARTICLE Lactate vs. CO2 in wounds, sickness, and aging; the other approach to cancerA study looking at radiotherapy with carbogen and nicotinamide for prostate cancer (PROCON)

H2 Gas:

Frontiers | Hydrogen Gas in Cancer Treatment | Oncology

Does H2 Alter Mitochondrial Bioenergetics via GHS-R1α Activation? - PMC

Molecular hydrogen suppresses superoxide generation in the mitochondrial complex I and reduced mitochondrial membrane potential - ScienceDirect

Hydrogen Gas from Inflammation Treatment to Cancer Therapy | ACS Nano

Hydrogen Water - Insanely Strong Reaction | Ray Peat Forum

Ascorbic Acid:

Vitamin C: Oral vs. Intravenous, Immune Effects, Cancer, Exercise Adaptation & More

Intravenous Vitamin C: Pathway to a New Therapy to Save LivesTherapeutic Use of Vitamin C in Cancer: Physiological Considerations - PMC

Cancer Perspective:

Stress-induced mutagenesis: Stress diversity facilitates the persistence of mutator genes - PMC

Diabetes and Cancer - PMC

Somatic Mutation Theory - Why it's Wrong for Most Cancers 

Adult Obesity Prevalence Maps (best in Colorado, but not great anywhere)

The somatic mutation theory of cancer: growing problems with the paradigm

Analyses of repeated failures in cancer therapy for solid tumors: poor tumor-selective drug delivery, low therapeutic efficacy and unsustainable costs

Ancient oncogenesis, infection and human evolution - PMC

Comparative analysis of cancer genes in the human and chimpanzee genomes - PMC

https://www.eurekalert.org/news-releases/652836

The Past, Present, and Future of Cancer Incidence in the United States: 1975 Through 2020 -

Bissell Lab

Dangers of sadistic science: Determinism vs process thinking 

Barbara McClintock - Nobel Lecture

Cancer: Disorder and Energy

Mina Bissell: Experiments that point to a new understanding of cancer | TED Talk

Dance to the Tune of Life

Stress Management: How Cells Take Control of Their Transposons

cancer

Testosterone for Life: Recharge Your Vitality, Sex Drive, Muscle Mass, and Overall Health How You and Your Doctor Can Fight Breast Cancer, Prostate Cancer, and Alzheimer' s

Potassium:

Potassium, sodium, and cancer: a review

“The cancer-causing drug dimethylhydrazine increases sodium and decreases potassium in the cells, whereas, for example, indomethacin, an anticarcinogen, has the opposite effect. In aging potassium leaves the cells, sodium enters them, and the rates of cancer increase. Patients with hyperkalemic diseases (Parkinson, Addison) have reduced cancer rates, and patients with hypokalemic diseases (alcoholism, obesity, stress) have increased cancer rates.”

A medical application of the Ling association-induction hypothesis: the high potassium, low sodium diet of the Gerson cancer therapy

Harnessing T-cell “stemness” could enhance cancer immunotherapy

A pilot study of potassium supplementation in the treatment of hypokalemic patients with rheumatoid arthritis: a randomized, double-blinded, placebo-controlled 

Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling | Cell Death & Disease

Potassium bicarbonate and D-ribose effects on A72 canine and HTB-126 human cancer cell line proliferation in vitro (Results on A72 cells indicate the K+ uptake could be determinant either to arrest or to slow down cell growth. )

Does dietary potassium intake associate with hyperkalemia in patients with chronic kidney disease?

Potassium supplement ameliorates salt-induced haemostatic abnormalities in normotensive subjects

Chronic potassium depletion increases adrenal progesterone production that is necessary for efficient renal retention of potassium

The significance of glucose, insulin and potassium for immunology and oncology: a new model of immunity

Chronic Ingestion of Sodium and Potassium Bicarbonate, with Potassium, Magnesium and Calcium Citrate Improves Anaerobic Performance in Elite Soccer Players

COX Inhibition:

Potential use of COX-2–aromatase inhibitor combinations in breast cancer

Anti-Inflammatory Agents for Cancer Therapy - PMC

Carbonic Anhydrase Inhibition

Carbonic anhydrase inhibitor - Wikipedia

Abstract 2015: Interplay of the pH regulator, carbonic anhydrase IX and the glutamine transporter, ASCT2 in hypoxic tumor microenvironment | Cancer Research

The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond

Acetazolamide and Breathing

Acetazolamide used for treating Glaucoma 

Evaluating off-label uses of acetazolamide

Carbonic anhydrases: novel therapeutic applications for inhibitors and activators 

Thiamine vs Cancer

“fursultiamine significantly decreased vascular leakage and lesion size, as well as the numbers of both choroidal and retinal inflammatory cytokines”

Fursultiamine Alleviates Choroidal Neovascularization by Suppressing Inflammation and Metabolic Reprogramming

[Genesis of tumor metabolism by vitamin B1 deficiency (thiamine deficiency)]

MECHANISM OF THE ANTICONVULSANT ACTION OF ACETAZOLEAMIDE, A CARBONIC ANHYDRASE INHIBITOR | Journal of Pharmacology and Experimental 

High-dose vitamin B1 reduces proliferation in cancer cell lines analogous to dichloroacetate

Abstract 2015: Interplay of the pH regulator, carbonic anhydrase IX and the glutamine transporter, ASCT2 in hypoxic tumor microenvironment | Cancer Research

The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond

Carbonic Anhydrase Inhibitors and Epilepsy: State of the Art and Future Perspectives

Chapter 13: Carbonic Anhydrase IX as an Imaging and Therapeutic Target for Tumors and Metastases - PMC

Carbonic Anhydrase IX Inhibitors as Candidates for Combination Therapy of Solid Tumors

Carbonic anhydrase inhibition with natural products: novel chemotypes and inhibition mechanisms

Phenols and Polyphenols as Carbonic Anhydrase Inhibitors - PMC

A Phase 1 Study of SLC-0111, a Novel Inhibitor of Carbonic Anhydrase IX, in Patients With Advanced Solid Tumors - PMC

The Effects of Thiamine Tetrahydrofurfuryl Disulfide on Physiological Adaption and Exercise Performance Improvement

Vitamin B1, anti-estrogenic, pro-DHT, anti-serotonin, pro-dopamine » MENELITE

New natural product carbonic anhydrase inhibitors incorporating phenol moieties

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

Natural Product Polyamines That Inhibit Human Carbonic Anhydrase

Stress & Cancer

Impact of stress on cancer metastasis - PMC

Melatonin

High Dose Melatonin Therapy - An Ideal Adjuvant Anti-cancer Therapy

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis 

Oral administration of melatonin counteracts several of the effects of chronic stress in rainbow trout

Melatonin inhibits lung cancer development by reversing the Warburg effect via stimulating the SIRT3/PDH axis - Chen - 2021 - Journal of Pineal Research

The underlying mechanism of MLT was related to reprogramming cancer cell metabolism, accompanied by a shift from cytosolic aerobic glycolysis to oxidative phosphorylation (OXPHOS). These changes were accompanied by higher ATP production, an elevated ATP production-coupled oxygen consumption rate (QCR), higher ROS levels, higher mito-ROS levels, and lower lactic acid secretion.

Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects - 

Melatonin for the prevention and treatment of cancer - P

Collectively, melatonin has exhibited inhibitory effects on both ER-positive and ER-negative breast cancers. Melatonin's anti-breast cancer effect was not only mediated by its interaction with both the estrogen receptors and the melatonin receptors, but also through activating various receptor-independent and estrogen-independent signaling pathways. Given the wide spectrum of melatonin's action on breast cancer, coupled with its low toxicity, it could be considered as a potential therapeutic choice for prevention and treatment of breast cancer.  Prostate cancer is the second most frequently occurring cancer and the fifth leading cause of cancer mortality in men . It was found that melatonin at pharmacological concentrations could inhibit cell growth of both androgen-dependent and androgen-independent prostate cancer, through various mechanisms.

Lipid Lowering - Higher Cholesterol Reduces Cancer Risk

cancer | Dr. Malcolm Kendrick

Progesterone

Preventing and treating cancer with progesterone.

Progesterone and Potassium

Chronic potassium depletion increases adrenal progesterone production that is necessary for efficient renal retention of potassium

Progesterone receptor modulates estrogen receptor-α action in breast cancer - PMC

Influence of Progesterone on the Sodium and Potassium Concentrations of Rat Uterine Fluid Investigated by Microdialysis

Acute and chronic effects of progesterone and prolactin on renal function in the rat. - PM

Apigenin as an anticancer agent

Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF-1alpha protein

Apigenin enhances skeletal muscle hypertrophy and myoblast differentiation by regulating Prmt7

Iron & Inositol

Lactoferrin's Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action - PMC

Iron and cancer: more ore to be mined | Nature Reviews Cancer

Aromatase Inhibition

Steroidal inhibitors that have been developed to date build on the basic androstenedione nucleus. Nonsteroidal aromatase inhibitors can be divided into three classes:..., and flavonoid analogs. 

Androsterone - A Potent Steroidal Aromatase Inhibitor | Ray Peat Forum

The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture

Frontiers | Estrogens and Their Receptors in Prostate Cancer: Therapeutic Implications | Oncology

Aromatase and prostate cancer

The anti-aromatase effect of progesterone and of its natural metabolites 20alpha- and 5alpha-dihydroprogesterone in the MCF-7aro breast cancer cell line

Potential use of COX-2–aromatase inhibitor combinations in breast cancer

From Nature

Isoflavones made simple – Genistein’s agonist activity for the beta-type estrogen receptor mediates their health benefits

Resveratrol and Cervical Cancer: A New Therapeutic Option?

HBOT

Hyperbaric oxygen therapy and cancer—a review - PMC

Ant-Inflammation

Anti-Inflammatory Agents for Cancer Therapy - PMC

Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin - 

Aspirin and cancer survival: a systematic review and meta-analyses of 118 observational studies of aspirin and 18 cancers - ecancer

Lithium

The Relationship Between Lithium and Cancer Proliferation

Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study

Frontiers | Systems Biology Understanding of the Effects of Lithium on Cancer | Oncology

Lithium inhibits tumor lymphangiogenesis and metastasis through the inhibition of TGFBIp expression in cancer cells | Scientific Reports

FAO

Fatty acid oxidation: An emerging facet of metabolic transformation in cancer

Derivative of vitamin B3 prevents liver cancer in mice -- ScienceDaily

Solasonine 

Evaluation of Solasonine Content and Expression Patterns of SGT1 Gene in Different Tissues of Two Iranian Eggplant (Solanum melongena L.) Genotypes - PMC

Patent Law

Nature-Based Products 

]]><![CDATA[Pre-Crisis Protocol]]>https://www.revfire.us/p/pre-crisis-protocolhttps://www.revfire.us/p/pre-crisis-protocolWed, 30 Mar 2022 01:16:03 GMTToday is my 39th birthday so in conjunction with health coaching discussions I’ve had with friends and family I’m going to implement another anti-aging modality as I approach 40.  If it all works out I would never biologically hit 40. I still have no significant desire for a sports car as I turn the corner, even if I had the expendable money it seems like the absolute wrong advertisement. Me, I'd rather simply start or perhaps more aggressively continue, rewinding the biological clock. 

Modest goals right. 

For no great reason I’ve been waiting on trying one of the best candidate protocols for antiaging the TRIIM protocol. Patient’s in the TRIIM and TRIIM-X use growth hormone in conjunction with metformin, DHEA, Vitamin-D & Zinc to then experience soft tissue repair and regrowth of vital organs while reducing fat and inflammation. Subjectively subjects discuss experiencing increased energy and mood. When they are tested for biological age they reduce age faster biologically than they age. Given that the epigenetic ages seem to reduce faster as the trial goes on. I have expectations to continue my proxy protocol for 18 months to 24 months before reassessing. Instead of growth hormone I intend to take GHRH (growth hormone releasing hormone) and (growth hormone releasing peptides) which are about 1/10th the cost of growth hormone and arguably safer. While I can get metformin I will use berberine, because it seems to have very similar benefits while being easily available over the counter.  

For anyone who would like to follow along here is the exact protocol costing just under 150$ per month. Not an extreme price to pay if it actually makes us younger.  Note: The lead researcher Greg Fahy says he’s having good success with women in his TRIIM-X trial though the numbers are low and they were not in the TRIIM original study. I would imagine the GH dosing would need to be adjusted for women from other research indicating women have a less pulsatile GH secretion.  If any of my women friends or family want me to dig more on this let me know...I’m happy to make an update.

CANLAB’s CJC-1295 and Ipamorelin combination: 

Approximately 1 vial monthly.  Dosing 1 day off per week (~250 mcg GH precursors/evening). 

Source: cjc-1295-mod-grf-1-29-3-mg-ipamorelin-4-5-mg-combo/

Cost: $80/mo

Renue by Sciences LipoBerberine: Approximately 2 bottles every 3 months

1x 150 mg 2x per day.

Source: lipo-berberine

Cost $35/mo

Life Extension DHEA: 50mg/day

Source: dhea

Cost: $8/mo

Now 7-keto-DHEA:25mg/day

Source: 7-keto-dhea

Cost: $5/mo

Vitamin D: 10,00 ius/day in olive oil capsules

Source: various

Cost: ~ $3/mo

Zinc Picolinate: 30mg/day

Source: Mom’s organic grocery

Cost: ~$2/mo

References:

Did a recent study show we can reverse aging? - Peter Attia

Thymus Regeneration, Immunorestoration, and Insulin Mitigation Extension Trial - Full Text View - ClinicalTrials.gov

#52 - Ethan Weiss, MD: A masterclass in cardiovascular disease and growth hormone - two topics that are surprising interrelated - Peter Attia

Older People Grow 2.5 Years Younger - Life Extension

Reversal of epigenetic aging and immunosenescent trends in humans - Fahy - 2019 - Aging 

My Theory Of Aging | Dr Greg Fahy Interview Series

TRIIM Drug Protocol | First Human Aging Reversal Trial | Dr Greg Fahy Episode 2

TRIIM - Growth Hormone & Safety Metrics | Dr Greg Fahy Episode 3

TRIIM-X - 2nd Phase Clinical Trial For Reversing Human Aging | Dr Greg Fahy Episode 4

How To Improve On Our Thymus Health | Dr Greg Fahy Episode 5

TRIIM-X - The Next Steps | Dr Greg Fahy Episode 6

Promising Anti-Aging Therapies | Dr Greg Fahy Episode 7

E5 On Dogs Project: Validating The 54% Reduction In Epigenetic Age | Dr Greg Fahy Episode 8

My Longevtiy Protocol | Dr Greg Fahy Episode 9

]]><![CDATA[Politics & Parasite Stress]]>https://www.revfire.us/p/politics-and-parasite-stresshttps://www.revfire.us/p/politics-and-parasite-stressSat, 12 Feb 2022 14:16:40 GMT"You still hear people say that the old South will rise again, but I doubt it has a chance unless disease prevalence goes up dramatically." R. Thornhill

Political Emergence

The fundamental energy dynamics of a human cell and the aggregations we call bodies to scale up into all the psychological and social dynamics we observe and participate in. Take democracy: modern democracy seems to have naturally emerged through the middle ages from various forms of councils, with monarchs often requiring their nobility to determine some laws and a tax rate. If we look at the recent past in the west, it might seem like a trajectory of accumulated wisdom, but I think that is mostly the wrong way to see democracy emerge. 

The Iroquois nation had its own model of representative government, and the founding fathers of the United States incorporated some of the elements into the design of our government. It turns out the Iriquoi tradition dates back to around 1200 AD. Given the complete separation of social histories, we need to jettison the idea that the specific lineage of ideas about government is of much or any importance. The emergence or re-emergence of democracy is borne less from the accumulation and spread of the ideas than from the state of the bodies considering and refining those ideas. Otherwise, where did the Iroquois model come from, where did the Greek model come from and how does it come and go? At some point, it always comes from the vacuum of creativity aimed at trying to produce social harmony. The monarch’s outsourcing a tax rate to their council was better thinking about what would preserve stability...it was more enlightened self-interest. That insight comes from a change in material physiological circumstances, which favor a predisposition to peace and shared prosperity. It takes a lot of mental and emotional capacity to realize the benefits of sharing power and responsibility.

Democracy and other governance structures are not typically seen as within the scope of biology, yet they are composed of bodies. Governance structures can, and I think, should be seen as emergent biological phenomena which require an appropriate population and density with high enough physiological health and intelligence. Upon those foundations, those who can intellectually and emotionally afford to begin considering various peaceful means of arbitrating political decisions, including succession planning for society's leaders. 

The American Revolution had embedded biological foundations. By 1776 North American populations had higher living standards than contemporary Europeans. During the early colonial period, the British male height averaged 5’5’’ inches, while Native American men on the eastern seaboard were around 5’8” feet tall. As the new settlers expanded for a few generations, they also got healthier and taller. At the time of the American Revolution, men’s average height had grown to 5ft 8in while the British male height remained at 5’5”. With their nutritional and energetic abundance, the fertility of American families at seven children per couple also outstripped England, which had (only) 5 children per couple. My point with all this is that with improved conditions came a significant enough change in attitude towards increasing rights and liberties for a broader population. The ideas encountering those minds also came from the metabolically enhanced and caffeinated minds exchanging ideas and ideals in the European salons. Yes, the institutions need to be discovered or invented, but there is a requisite capacity of minds for generating and appreciating them. The condition of the bodies of society are foundational. 

Parasite Stress Theory 

A strong candidate for the most critical factor driving the expression of personality and, thus, political preferences is stress, and in particular, stressors that affect the perceived susceptibility to disease. The parasite-stress theory of values was defined by evolutionary biologist, Professor (Emeritus) Randy Thornhill.  Regional variations in pathogen load are the ultimate cause of population-based personality shifts and the political regimes that emerge from such personalities. The theory is well supported by facts on the ground and around the globe. In his own words: 

First, high parasite stress evokes a value system of collectivism in which individuals are authoritarian, xenophobic and ethnocentric, with a disregard for—and in the extreme, a moral disgust about—the rights, liberties and well-being of out-group members, including those lower in the established social hierarchy. Such out-group individuals are viewed as invalid members of the in-group(s) in power and maybe dehumanized and disenfranchised. This conservative ideology includes negativism toward and oppression of ideas and other innovations perceived to threaten traditional norms and values and hence is a barrier to the creation and diffusion of novel ideas and technologies. As we have emphasized, collectivist ideology is a defence against novel contagion harbored in out-groups and a means to manage infectious agents that arise within the group. 

Second, low parasite stress evokes a value system of individualism that includes anti-authoritarianism, tolerance, validity and trust of out-groups; a willingness to interact with, support, and empathize with different others; and a high regard for the rights and freedoms of the majority, including those of lower social class or with different values, religious convictions, languages, and ethnic identities. In extreme form, this is an ideology without prejudice toward any people because all are considered sentient beings with morality, autonomy, and inalienable worth. Individualist ideology promotes and rewards innovations and includes a willingness to consider and adopt them, even those from out-groups. Liberal values serve to provide benefits to individuals via promoting out-group interaction and the associated exchange of goods and services, the adoption of functional innovations of out-groups, and the establishment of social alliances with out-groups. 

The empirical prediction that follows from these considerations is that, across the globe, the degree of democratization will correlate negatively with parasite stress and correlate positively with individualism (and negatively with collectivism). Said differently, as parasite stress and collectivism increase across nations, so, too, will the degree of autocracy.

The two arguments I have with Randy’s position are: 

1. I consider parasite stress as only one of many values-related stresses. To say it another way: stress physiology often compromises the immune system. It plays out physiologically through mechanisms such as metabolism, inflammation and central nervous system activation.  With an overactive nervous system and metabolism reduction, people will have compromised immune systems and be more susceptible to parasites.

2. Right-wing-focused authoritarian surveys overrepresent surveys for authoritarianism. The whole field of psychology is almost entirely made of people sympathetic to the left and as such, has done much less research on the left’s seemingly equivalent potential to exhibit authoritarian traits, including:

  • Anti Hierarchical Aggression – the belief that those currently in power should be punished, the established order should be overthrown, and that extreme actions, such as political violence, are justifiable to achieve these aims.

  • Anti Conventionalism – the rejection of traditional values, a moral absolutism concerning progressive values and concomitant dismissal of conservatives as inherently immoral, and a need for political homogeneity in one’s social environment.

  • Top-Down Censorship – preferences for the use of governmental and institutional authority to quash opposition and bar offensive and intolerant speech.

In recent years, however, research into the left-wing form of authoritarianism has been ramping up. Particular sentiments of left-authoritarians are captured with questions like: 

“I should have the right not to be exposed to offensive views”

“Getting rid of inequality is more important than protecting the so-called ‘right’ to free speech,”

“I cannot imagine myself becoming friends with a political conservative.”

Traits shared by both political extremes:

“preference for social uniformity, prejudice towards different others, willingness to wield group authority to coerce behavior, cognitive rigidity, aggression and punitiveness towards perceived enemies, outsized concern for hierarchy, and moral absolutism.”

I have yet to find a paper describing the physiology of the two types - if there is any. My guess is that if someone expressing a high degree of authoritarianism feels they are reproductively benefiting from the existing hierarchy, they will aim to bolster it, while if another authoritarian is being reproductively denied by the social structure, they will seek its destruction, but that is only my unsubstantiated hypothesis. If true, however, it would suggest that there might be an endocrine profile of positional security and one of positional insecurity, which to me seems at least plausible and consistent with other primate studies. Curiously, Thornhill and Fincher’s 2007 study associates low secure childhood attachment to liberalism and high secure childhood attachment to conservatism. If valid, this finding leaves me a lot to unpack and iron out in terms of the timing and effects of different types of stress. My intuition would be that more secure attachment would lead to more resistance to contagion and more openness to novel people, places and pathogens, so either the work is inconsistent or my understanding is flawed.

In any case, both types of authoritarianism seem ascendant in more recent times. Neither rise can very well be explained by a rise in parasite exposure (before the recent pandemic), so we must assume, as I do, that other psychobiological factors such as a general increase in physiological stress are affecting people’s psychology. The mind is changing when the body becomes more susceptible to disease. When susceptibility increases, the behavioral immune system expresses contagion-risk-reducing emotions and values, values and emotions consistent with authoritarianism. 

Given this psycho-bio-evolutionary-existential situation, we would benefit from a new biologically based political science, perhaps a ‘biopolitics’. We can now understand that stressed body states drive inclinations towards collective, authoritarian behaviors on either political extreme. We do not yet understand why someone might be moved one way or another, but both extremes are expressing increased disgust, fear, anxiety along with expectations and enactments of violence. Unfortunately, the increased anxiety in a polarized culture seems to have very clear feed-forward mechanisms perfectly in line with the dynamics of all human conflict escalations. One party feels angry or anxious and blames the other and, in doing so, creates the fulfilment of their prophecy or expectations because the other reacts to the expressed anxiety by becoming defensive with return criticisms and the cycle repeats. Historically it repeats until there is organized physical violence with a clear victor who often enough perpetrates genocide. 

Perhaps civil war seems impossible in a world with golden arches and smiling Ishtar on every corner. Still, I follow various credible thinkers articulating the trajectory where war is increasingly likely. These thinkers don’t attend much to the biological substrate of the situation, but the larger social patterns seem clear enough for their predictions. Ray Dalio, one of the world’s most successful hedge fund managers, only last week sent an essay with this in the first paragraph: 

“the US appears to be on a classic path toward some form of civil war”

Consistently, the Pew Research Foundation has been tracking the last two decades of increasing division:

Peter Turchin, a mathematical historian, has been tracking broad indicators of stress and forecasting the impending division of society for a few decades: 

“Popular immiseration has been increasing for decades. I have written before how shocking it was for me to see such Malthusian indicators of stress as declining life expectancy, which turned down before Covid-19”

“The overall trend towards immiseration is very worrisome, especially because it is broad-based. It’s especially worrisome because the previous immiseration period almost perfectly coincides with the period of social turbulence and political violence”

Peter’s process is closer to mine as he focuses on stress indicators that include health status, family formation and age of childbearing.  Below are his aggregate indicators. We only see similar situations existing around and after the (first) civil war and before the revolutionary war. Tracking the blue (or green) line, well-being has been trending down since the 60s:

Years ago, I thought extreme views were based on features or bugs of social media and perhaps types of reduced exposure childhoods that limited play and humor.  While those may be factors, I am now disposed to think that a personality that attaches to extreme views is much more based on the person’s present material reality. Despite all our advances in technology, we’ve begun regressing in both health and intelligence at the broadest social level. Many Americans are much worse off physically and psychologically than they would have been a generation prior. Mean incomes through stagnant do not capture the declines in health nor the new medical uses of those stagnant incomes. Changes in the body are changes in the mind, and our stressed and often disease-burdened bodies are sending very important reminders of challenging conditions, conditions that foretell even tougher times ahead. 

Selected References:

The_Parasite_Stress_Theory_of_Values

What is the relevance of attachment and life history to political values?

How Experts Overlooked Left-Wing Authoritarianism - The Atlantic

The Germ Theory of Democracy, Dictatorship, and All Your Most Cherished Beliefs

Parliament of England - Wikipedia

The Connection Between Disease and Authoritarianism | Cato Institute

Clarifying the Structure and Nature of Left-Wing Authoritarianism

Democracy and the Iroquois Constitution | Field Museum

AMERICAN MEN OF 1776 SAID TO HAVE STOOD TALL - The New York Times

United States: fertility rate 1800-2020 | Statista

United Kingdom: fertility rate 1800-2020 | Statista

For most U.S. workers, real wages have barely budged in decades

The Rising Risk of Civil War: Following in the Footsteps of History

Peter Turchin Age of Discord II

Political Polarization in the American Public | Pew Research Center

]]><![CDATA[Cyclical Discomfort]]>https://www.revfire.us/p/cyclical-discomforthttps://www.revfire.us/p/cyclical-discomfortFri, 04 Feb 2022 00:50:47 GMTI hope this to be a compelling, useful story as far as I can tell about women’s health. I’ve previously ventured into this topic area, but perhaps without appropriate personalization. It’s hard to personalize pain you haven’t suffered, but probably no man is far removed from the suffering of the women in his life, I’m no exception. I’m writing to female kith and kin whose ripples of pain have had and have me digging for better understanding. I’m also writing to other men who are also hurt deeply by the state of the socio-biologic system we find ourselves in. I hope as much as I am able, that we may wake up to both the perversity of our status quo and wake up to the insight and potential for agency to turn it all around. Nature has laid down the rules for us to seek from which we can cast off of our ignorance. 

Women’s cycles and fertility are temperature expressive and dependent. The metabolic and temperature frameworks I’ve written about in, The Heat of Attachment, Winter, Thyroid and Cardiovascular Health set the groundwork for understanding. However; the physiology of menstrual cycles is a place of important dynamics to learn from and is likewise rich for applications of the foundational principles. 

A very large and rapidly growing percentage of the female population suffers from pain, inflammation and potential fertility issues associated with menstrual endocrine dysregulation. While this is surely to be in evidence for some women in some cases of evolutionary history, it is very likely at a maximum for absolute and relative amounts in the current environment.  Menstrual suffering is very likely surging similar to what we see in the CDC tracking of obesity. That is it was very rare and is now the new normal. However, it is almost certainly a much less discernible issue. No one really knows if their experience is “normal” and the health system seems to support only interventions that are palliative with the potential escalation to surgical removal. Which seems a barbaric example for the professions lack of knowledge. What our health professionals might aim for as physiologically ‘normal’ in today’s environment is evolutionarily abnormal.  And another ready answer for most MDs is likely to be use of some type of contraceptive or NSAIDs. Finding a contraceptive might be a way to some relief but not without some relatively silenced side-effects (see The Pill Changes Everything for more details).

Estrogen acting through the body is associated with dissipating energy through vasodilation, while progesterone is associated with the core body temperature rising. While much of the reproductive literature seems mired in confusion and subterfuge the temperature basics are very clear. Estrogen concentration increases and drops the body temperature and while progesterone increases the body temperature also increases. They both act on temperature by modifying the amount of available active thyroid. Estrogen increases proteins that bind and block thyroid, while progesterone promotes more free thyroid. The temperature chart over the cycle is quite consistent with that story. The most energetically demanding period is when the core temperature and overall metabolism is increased and estrogen is both behaviorally and physically giving off heat. 

It’s no surprise that this occurs just at ovulation. In the chart below you can see that estrogen increasing drives the low temperature and the progesterone increase is consistent with the increase in temperature.

Where it gets a little murky is with the cause of premenstrual mood and bodily sensation. With a perspective related to thermoregulation and metabolism we can put together the picture being hidden. Many official sounding sources seem to implicate progesterone in increasing PMS symptoms which I think is probably (almost certainly) wrong and runs counter to many other practitioners using progesterone to alleviate the very same menstrual symptoms. Given what we know about heat and thyroid association with progesterone, I think those anti-progesterone ideas are generally inconsistent. Much of the confusion seems to come from studies not discriminating between actual progesterone and the various progestins invented to make money off the same actions a nonpatentable hormone progesterone does better, progestins like methoxyprogesterone. 

To clear up the confusion here are pieces of the puzzle laid out:

  • From work on thermoregulation we know that a loss of body heat will drive a desire to seek out heat, calories and connection, a lack of body heat feels a lot like loneliness.

  • The symptoms of hypothyroid are remarkably similar to symptoms of premenstrual syndrome: stress, overwhelm, depression, tearfulness, mood swings, ease to anger

  • High cortisol production competes with progesterone for production, but unlike progesterone which causes steady blood sugar, cortisol causes swings in blood sugar and reduces insulin, and insulin sensitivity. Cortisol allows the body to use glucose, protein and fat rapidly for highly immediate stress response. 

  • Sufficiently high progesterone is necessary for the next cycle’s estrogen receptor sensitivity to be reset, lack of which can further increase estrogen imbalance  

  • Anecdotes from those who manage their own work schedules suggest that taking one to two days off work, reducing stress, coincident to when PMS or cramping would occur, seems to dramatically reduce if not eliminate pre and menstrual symptoms.

  • Many functional MDs and naturopaths use bio-identical progesterone or vitex during the luteal phase to ameliorate symptoms of PMS and menstruation. 

  • Vitex increases luteinizing hormone, progesterone and dopamine while reducing estrogen, prolactin, and follicle stimulating hormone.

  • Real progesterone is a precursor to allopregnanolone. 

  • Allopregnanolone is one of the most important hormones promoting positive mood and has relaxing and soporific effects. 

  • Progesterone is known to reduce inflammation, reduce prostaglandins, inhibit endometrial growth and thin and stabilize the endometrium. 

  • Cortisol production increases prostaglandin production while progesterone decreases it

  • Progesterone is used to treat endometriosis.

  • When less endometrium is grown, bleeding is less and removal is more complete

  • Increasing metabolism for a sustained increase in temperature and reducing cortisol requires an increase in energy from the diet after ovulation. 

  • Cortisol and insulin are antagonists, meaning higher carbohydrates would reduce cortisol and so too prostaglandins along with premenstrual and menstrual symptoms 

  • Omega-6 oils are extremely supportive of prostaglandin synthesis which helps reduce thyroid and prepares mammalian bodies for hibernation (see Winter, Thyroid and Cardiovascular Health)

  • Negative menstrual symptoms are highest when heat, thyroid, vitamin D, dopamine and progesterone are the lowest (Dec-Feb) in the northern hemisphere

What I think is going on follows. Firstly, premenstrual and menstrual issues seem to affect all women with variations of factors including age, bodily stress and inflammation, contraceptive use, and child status. Certainly genes also play a role, but the environment is so impactful and potentially unsupportive that we have a lot of options to exhaust before defaulting to a “bad genes” explanation. “Genes” is an easy go to for MDs who have no time to looking into research outside the pharmaceutically funded training courses. Also note that normal physiology in this decade of this century is not a good approximation of health status. Bodies are being attacked from multiple angles and it is highly likely that women are, on average, more sensitive to environmental conditions in order to unconsciously prevent investment in children when the environment is not conducive. 

Most work environments, including white collar ones, require a kind of constant vigilance that is probably not good for anyone, but will most influence those people that are more physiologically sensitive. The modern economy has also done much to disrupt the kinds of social bonds that humans depend on, and lacking those we should expect some anxiety as a new baseline. Simultaneously, various chemicals and lifestyle factors are driving estrogen dominance while the entire food supply system is focused on delivering ever more of the least quality, most inflammatory calories. All of these and more are working together against all of our well being.

Applications

Taking or applying exogenous progesterone is something that I recommend to balance out the environmental deficits. Increasing one's active thyroid along with the increased calories to match is another good option. Many people are hypothyroid which leads to limited hunger and even the metabolic processes for proper digestion. I even do both progesterone and thyroid, even though menstrual management for me is irrelevant. Oxytocin is suggested in some of the literature for PMS and it’s more severe form PMDD.  Taking oxytocin is perfectly consistent with metabolic-thermoregulatory perspective. Oxytocin increases peripheral metabolism and feels like, from both the literature and personal experience, more confidence or less social insecurity. Cannabinoids THC-a and CBD are also suggested to be beneficial as anti-inflammatories and their potential for reducing stress. All of that said, the first place we should probably consider focusing our efforts is electrolytes. 

I have been amazed to find potassium as a ready solution for dysmenorrhea. 400 - 600mg of potassium gluconate daily and apparently the dysmenorrhea should disappear during the second cycle after starting. There is a lot more to learn about potassium, but that is a very cheap and ready option for those willing to venture a try. Evolutionary peoples almost certainly ate much more potassium than we do. Magnesium has some evidence behind it and should be managed for all types of health ailments including menstruation. Proper amounts of both magnesium and potassium will reduce blood pressure. Premenstrual discomfort seems significantly related to the body's water balance and blood pressure as it comes with a rise in blood pressure of 20 -30 mm and associated water retention. Both potassium and progesterone oppose cortisol. Cortisol like aldosterone is sodium retaining and potassium excreting, and opposing it increases the balance towards sparing potassium and excreting sodium.  Water will go along with the sodium as will much of the swelling and increased blood pressure. The body will also return to a more insulin sensitive and reduced stress state. Below is a diagram of potassium’s immediate effects including reducing sympathetic nervous system and increasing the metabolism through insulin excretion and vasodilation:

 Below is a report from someone who self treated her PMDD:

“Eating a potassium-rich diet, which I had always done, did not help my symptoms.

I knew taking potassium supplements was medically safe for me, so I began taking them every day beginning very early in my cycle. To my surprise, my stamina and energy level dramatically improved. This occurred within the first week of beginning the potassium when it was still my non-symptom follicular phase. In retrospect, I had become so accustomed to my stamina being low all the time that it seemed normal compared to the extreme fatigue I experienced during my PMDD time. Over the next three months, my symptoms gradually decreased until I was completely free of PMDD.”

Seems kind of miraculous but when considering the concentration of potassium in living cells and the food supply’s perpetual move towards delivering less and less fresh cells be they from meat, dairy, fruits or vegetables. All perishable foods have potassium because potassium is retained in the interior of cells as part of the living state’s energy management system. Making processed food essentially breaks or denatures cells and injury leads to a rapid loss of ATP and potassium. Top foods high in potassium include: greens, potatoes, milk, white button mushrooms, bananas and salmon.  While doing this research I am taking at least 600 mgs daily of potassium gluconate - while also being cautious about using NSAIDs which can retain potassium and cause hyperkalemia. So far I only notice that my blood pressure is lower as is my blood sugar and I suspect it takes time to adjust down the insulin response to food with a higher potassium diet.  

Behavioral:

I’ve heard very reliable anecdotes from friends who have completely mitigated the physical and emotional distress around menstruation by simply not working and taking the premenstrual days a bit easier. This makes lots of mechanistic sense as reducing cortisol and minimizing the calorie deficit that can easily kick in after ovulation when the body actually heats up to keep the potential bun warmer. Some countries like Japan, and a few companies like Nike actually seem to have some sensible policies around this. I was quite surprised in fact. I imagine however, that all of my readers will not have known a work environment beyond sole proprietorships that make this easy. Other ideas I’ve seen include increasing touch and physical intimacy for the oxytocin as mentioned briefly above. To be mildly cynical and hopefully slightly humorous, in experience, confidential notes from other men, and cultural lore it seems the lack of awareness or concern for the whole causal scheme depicted above as well as projection of the felt discomfort onto unwitting proximal subjects drives the likelihood of this type of physical intervention towards zero. From a partner’s point of view, it’s probably best to get the discomfort down through the appropriate metabolic inputs as an initial step. 

Some Realted Products: 

Delune - CrampAid

KrampAid - up to 4 grams of potassium!

OvuFirst™ Wearable Fertility Monitor - Starter Pack

Selected References:

The Purpose of Potassium – Dr.Berg

Progesterone therapy increases free thyroxine levels--data from a randomized placebo-controlled 12-week hot flush trial

 https://doi.org/10.1016/B978-0-323-43044-9.00166-7

Effect of progesterone, cortisol and dehydroepiandrosterone-sulfate on prostaglandin production by cultured human myometrial cells

https://europepmc.org/article/med/32789612

https://www.myfooddata.com/articles/food-sources-of-potassium.php

Menstrual leave - Wikipedia

Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model

Evaluating the effect of magnesium and magnesium plus vitamin B6 supplement on the severity of premenstrual syndrome

Progesterone Summaries - Progesterone Deceptions - Progesterone Supplementation - Dosage of Progesterone

“After the intervention, the mean score of PMS significantly decreased in all the three groups (p < 0.05). The decrease was the greatest in the Mg plus vitamin B6 group, and was the least in the placebo group.”

PMDD and Potassium | IAPMD

Potassium: A New Treatment for Premenstrual Syndrome - Beckie E. Takacs, MS

evolutionary biology of endometriosis | Evolution, Medicine, and Public Health | Oxford Academic

Revisiting the roles of progesterone and allopregnanolone in the nervous system: Resurgence of the progesterone receptors - ScienceDirect

Autonomic control of body temperature and blood pressure: influences of female sex hormones — Mayo Clinic

Frontiers | Negative Association Between Allopregnanolone and Cerebral Serotonin Transporter Binding in Healthy Women of Fertile Age | Psychology

“Premenstrual tension was aptly described by Dr. HE Billing in 1953 as irritability, depression and lethargy. “ Katerina Dalton MD 1969, The Menstrual Cycle

“Characteristically, patients with premenstrual syndrome have more than one symptom.  Apart from tension..commonest symptoms include are headache, asthma, hay fever, joint and muscle pain and backache” Katerina Dalton MD 1969, The Menstrual Cycle

]]><![CDATA[Cosmic Metabolism ]]>https://www.revfire.us/p/cosmic-metabolismhttps://www.revfire.us/p/cosmic-metabolismThu, 20 Jan 2022 03:37:45 GMT“It [The Second Law of Thermodynamics] is the only physical theory of universal content, which I am convinced, that within the framework of applicability of its basic concepts will never be overthrown.” 

-- Albert Einstein on Classical Thermodynamics

“Energy and life go hand in hand. If you stop breathing, you will not be able to generate the energy you need for staying alive and you’ll be dead in a few minutes. Keep breathing. Now the oxygen in your breath is being transported to virtually every one of the 15 trillion cells in your body, where it is used to burn glucose in cellular respiration. You are a fantastically energetic machine. Gram per gram, even when sitting comfortably, you are converting 10,000 times more energy than the sun every second.”

― Nick Lane, Power, Sex, Suicide: Mitochondria and the Meaning of Life

“Life’s purposeful nature, broadly understood, has thermogenic origins.”

― Eric Schneider & Dorion Sagan: Into the Cool Energy Flow Thermodynamics and Life

The deepest part of what I’m trying to convey is a sort of pattern of unfolding built into the nature of our universe. I find it hard to ignore the ideas of emergence where initial rules and conditions of a system dictate wildly unpredictable and complex outcomes, yet still retain some intelligible patterns and constraints throughout the levels of organization. For an example of emergence of unique but recognizable form the growth of a snowflake comes to mind. Given the right temperature, moisture, and particulate, a snowflake will grow with both patterns of similarity as well as individual uniqueness. Snowflakes like galaxies, stars, planets, and living cells emerge out of the substructures and rules of the cosmos. 

Looking into where physics becomes biology we find non-equilibrium thermodynamics, a field which describes natural structures, dissipative structures like hurricanes and biological cells. All far from equilibrium systems need a throughput of energy to maintain their structure and function. A hurricane's enormous energy comes from the temperature gradient between the sea and the cooler upper atmosphere. Biological non-equilibrium structures not only dissipate energy gradients but seek out gradients to further sustain themselves. Concretely, we animals and fungi seek out chemical gradients provided by other organisms, while plants grow and move toward the gradient of electromagnetic waves. 

We biological structures also reproduce and thereby innovate to create more structures further and faster degrading evermore gradients. In this light, evolution is a special, living case of the second law of thermodynamics. Evolution is an algorithm to find and exploit gradients more effectively as well as to push dissipation into novel territory where new exploitable gradients lie.

 “Living systems strive...to catch, store, and degrade gradients. Trends arise in both ecosystems and evolution, toward increasing number of species, more developed networks, increasing differentiation, increasing functional integration of thermodynamic flows, increasing abilities of organisms to adjust themselves to dwindling and changing gradients, and increasing capacity for dissipation” 

Evolution is considered to be blind, but the laws of physics constrain the spaces for energetic niche exploitation, and it seems the overall “purpose” of evolution is to increase dissipation. Presuming this correct, then the great paradox of life is to have temporarily stable systems generated and living in order to ever more rapidly diffuse order into chaos.

When put metabolically into comparison with the sun as Nick Lane has: “Gram per gram, even when sitting comfortably, are converting 10,000 times more energy than the sun every second.” Did you imagine that? Maybe he picked a good metric to favor humankind, but it sounds to me like something special is going on right in the living world in terms of thermodynamics. Perhaps romanticizing, I find this a very aesthetic way to look at the dynamic cosmos. Below is a graph of the evolution over time of respiration intensity. It does not include humans or our techno-economic footprints of energy usage which no doubt continue, if not accelerate the trend.

Our cells are massively dissipating energy, and what cells are the most metabolically by unit of mass? Brain cells, along with gut and liver, are the most metabolically active cells in the body. Intelligence is significantly linked to metabolism. Brain metabolism affords intelligence. Paradoxically to all of mainstream medicine, if we assume we want more intelligence we are opposing well entrenched ideology towards “health” because intelligence also happens to be positively correlated with higher HDL, LDL, VLDL and triglycerides. Intelligence also happens to be inversely associated with bilirubin which I have excess amounts of, and which might make you wonder why you should keep reading this beyond pity or charity.

In regards aging and metabolism, it’s been known for over a hundred years that children have metabolisms much higher than adults per unit of body weight.  Kids nine years and younger have nearly double the metabolism and therefore physiological CO2 than adults whose metabolism tends toward decline. While I couldn’t find the data I highly suspect the metabolic rate is likely highest in the womb where the warmth and the gas exchange process would keep the CO2, O2 and blood perfusion very high. After all, the fetus’s skin is not yet required to protect it or perform much in the way of insulation, so it can be fully perfused and stay in growth/repair mode. Relatedly, children’s severed fingertips can often grow back. Completely securing them in an airtight fixture allows the CO2 to build up and aids the process. Writing this, I find myself deeply curious if any epigenetic researchers are looking at the simple potential for CO2 concentrations to turn on further repair mechanisms at the gene or epi-genome level. When we are thinking about healing ourselves I suggest the womb as a good model for an ideal self healing environment, I imagine it looks a lot like the matrix pods, or perhaps float tank versions 10.0.

Studies showing deficiency, even mild deficiency of thyroid are very clear. Low maternal thyroid and low child thyroid are significant risk factors for very low intelligence. and the association of intelligence with cholesterol would also be consistent as thyroid is required for cholesterol synthesis, and cholesterol is integral to brain development, structure and function. Unfortunately for most of us modern people the fluoride in the water does have a significant effect on both thyroid and intelligence. Though the effect is contested, the chemistry is rather straightforward as fluoride or chloride readily replace the iodine required for thyroid production. And more unfortunately, using levothyroxine prior to and during pregnancy has not yet been shown to remedy the risk. Somehow doctors still call it benign hypothyroidism. I would also suggest that studies would do better if they used active thyroid instead of levothyroxine. Levothyroxine needs conversion by the liver which is dictated by...protein and thyroid levels. Often this is why some women will have no benefit from t4, levothyroxine.

Increasing maternal thyroid is only beneficial to a point. Women with both too high and too low of thyroid have less desirable outcomes in terms of IQ for their children. That is, increased IQ relates to higher metabolism. In an evolutionary sense I imagine that a high IQ requires a bigger more demanding brain and like a change in any physical characteristic poses evolutionary tradeoffs or risks. I think the maternal thyroid curve of effects makes sense considering that it is probably nutrient availability, especially glucose and temperature that are driving conditions for brain development.  A mother with too high of a thyroid level will be using up her glucose on her own processes. To that effect it is likely that progesterone is a critical hormone for fetal cognitive development. For starters, it’s associated with very positive cognitive and neurological effects in adults, and secondly it increases blood glucose. The supply level of glucose to the fetus is dependent on maternal progesterone levels. Progesterone levels will decrease with increasing maternal stress and reduced stress will allow for more progesterone. IQ happens to be associated will all markers of health later in life, and as such a reasonable indicator of overall brain health.

Through gestation, birth and childhood the energy state of both the person and the people around are important for the development of personality and sense of morality. The security of maternal warmth and nurturance as described in The Heat of Attachment will drive the organism's brain development and its initial expectation of the environment. This will set the stage for whether the child sees a world of threats or a world rich with resources and connection. I suggest that this imprint on the nervous system is key to understanding the emergence of both open societies and authoritarian eras and regimes. 

A critical component of an individual’s stress is the pathogenic load of the child and its kith and kin in community. To tie them together one has to make the realization that central and peripheral body heat and metabolism are critical for keeping the immune system healthy and pathogens at bay. A higher metabolism allows the immune system to more quickly respond to threats and to better access tissues as perfusion is increased with warmer body temperature. When metabolism decreases or pathogenic load increases the organism will become more energetically conservative. The lower the metabolism, or the lower the energetic balance, the more the organism will act to avoid further pathogen exposure and the less energy it will have for cognition. This is called pathogen avoidance and it's been verified in a variety of species and contextualized in humans as part of a behavioral immune system. 

The behavioral immune system is a suite of psychological tendencies that aim to protect us from disease spread. The behavioral immune system under load is behind many non-liberal values like xenophobia. As I’ve argued elsewhere the immune system is a critical, but only partial subcomponent of allostatic load or the body budget. Evidence seems to support that any increase in metabolic cost will drive similar psychological shifts from openness and curiosity towards fear and anxiety. This can be recognized in simple daily life: when we are injured, sick or stressed from external social or economic factors our curiosity shrinks and ideas become more rigid. From whatever norm we have, we feel less creative and less extroverted. If we feel bad enough internally we are much more liable to express that externally. To say the same thing from the opposite perspective, as our disease and metabolic loads decrease we will find ourselves expressing our personalities with more energy, more positivity, more openness and more tolerance for outsiders.

What I’ve tried to demonstrate is that there seems to be a sort of law of the universe from the big bang, into the origin of living cells and through evolution finding ever increasing metabolisms. Along with metabolism and respiration, cognitive capacity has increased. We use that cognitive capacity to both solve problems and just be or create beauty, but in either case to ever increase our energy throughput. While I expect that trend to continue over the longer run, it’s a bit of a drag to feel like we are living through the depths of a cognitive and metabolic depression. Here’s to hoping it resolves within our lives and most importantly that the negative trend does not positively feedback upon itself.

Selected References:

Into-Cool-Energy-Flow-Thermodynamics

Power-Sex-Suicide-Mitochondria-Meaning

The Expensive-Tissue Hypothesis: The Brain and the Digestive System in Human and Primate Evolution 

Brain metabolism predicts fluid intelligence in young adults -- ScienceDaily

Mild-thyroid-disorder-could-hurt-brainpower

Intelligence quotient in children with congenital hypothyroidism

Early Levothyroxine Treatment for Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy: The St Carlos Gestational and Thyroid Protocol

Hypothyroidism During Pregnancy Linked to Lower IQ for Child Early Diagnosis & Treatment May Help 

Thyroid Function in Early Pregnancy, Child IQ, and Autistic Traits: A Meta-Analysis of Individual Participant Data | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic

Relationship of the Thyroid with Intelligence and Personality

Levothyroxine Fails to Increase Iq In Offspring of Women With Subclinical Thyroid Disease

Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy | NEJM 

The interplay between thyroid and liver: implications for clinical practice

IQ in childhood and the metabolic syndrome in middle age

Metabolism as a guiding force for immunity | Nature Cell Biology

]]><![CDATA[The Heat of Attachment]]>https://www.revfire.us/p/the-heat-of-attachmenthttps://www.revfire.us/p/the-heat-of-attachmentSun, 16 Jan 2022 15:35:42 GMTOne major thing I feel I’ve learned in all my relationship efforts and reflections is that attachment to one's original attachment seems deeply ingrained. We may feel like we are adults with fresh starts able to re-invent the path relationships can take, but in fact we are more like an amalgamation of our former selves with the outward facing adult layers atop deep, dense and densely carved pre-verbal layers of our much younger selves. The first few years of life are critical.

 We become who we are by sensing and acting through the world of inputs in the womb and beyond. We build our core of personality in relationship to a mother’s attunement and her attunement or lack thereof is very valuable information for what kind of world we are just arriving in. Human threat system will turn on earlier than the threat, we have a built in survival bias. The direct provision of heat is very important to our physical and psychological development with deep connections between thermoregulation and attachment theory. 

A rather remarkable and convincing finding related by Hans Ijzerman in his recent publication of Heartwarming, How Our Inner Thermostat Made Us Human. Actual provision of physical warmth to an infant by its mother is a critical input to our mammalian, and human, attachment systems. Rat pups kept at appropriate temperature did remarkably better than others when they were separated from their mothers. This indicates the importance of the pure temperature element in the relationship. Mothers producing increased amounts of oxytocin go on to increase their peripheral temperature allowing more heat transfer to their pups or babies.  Less heat from less oxytocin or any other disturbance without some kind of substitution would mean a less beneficial development. 

Our thermoregulatory systems are impacted by social inputs throughout our lives. Even as adults we crave energy and heat compensation from a loss or absence of social support. We will turn down our metabolisms and peripheral temperatures when we are faced with a loss of social support. The evolutionary logic is that we will be less secure about future nutrients or other threats with a less robust social network which will drive our bodies to reduce metabolic output and conserve resources. The work on thermoregulation aligns well with research into oxytocin and metabolism more broadly, and is light years ahead of typical counseling or psychiatric paradigms. If true, it seems like a major breakthrough grounding both psychology and relational psychology in physiology with lots of ready applications and implications.

It happens to also be deeply consistent with the overall argument that social-moral behavior is significantly if not primarily driven by environmental metabolic conditions, especially the availability and use of energy. I argue that the energy throughput of individuals matters greatly in determining the aggregate behavior of groups and societies. To quickly see what I mean you can read my article On Locusts and War, or for a more extended look into the effects of nutrient access on social life consider reading: Climate, Catastrophe, and Faith by Philip Jenkins. Climate, Catastrophe and Faith is a powerfully important read which documents the impacts of climate change on historical religious behavior. While the author was trying to make a point about climate change he did a marvelous job of pointing out all of the major negative influences of historical cooling and essentially only positive effects of warming considering his focus on Europe during the middle ages. A similar more global analysis might find the psychosocial change that occurs with and before drought. I expect caloric deprivation from any source will cause similar stress physiology and psychology, but perhaps some difference would arise from the specific environmental features. At the moment I am wondering how I have not looked further into climate and the rapid spread of early Islam.

Returning to the topic at hand however, the theory of embodied social cognition and attachment if understood fully has massive implications for how we might manage our personal and social well being. As a recent personal example: I found myself reading Heartwarming while feeling both lonely and physically cold. For about a week around the winter solstice I found myself wondering what was happening such that I went from happy to lonely in very short order. I read about how we try to compensate for a lack of social attachment(s) by seeking warmth and vice versa, we also seek social attachment more in colder environments and seasons. I happen to be experiencing that and writing this as the nadir of my social life having moved in the winter during a pandemic to a suburb full of transient, commuting, fearful rule-abiding folk. After reframing the likely source and internal, I started thinking through all the supplements I take and how they might affect my body's temperature and calorie balance. For those of you who might not know, substances like quercetin which is good for immunity also suppresses thyroid and with it temperature and metabolism. I was taking it in consideration of COVID as a zinc ionophore, but in line with the thermoregulatory (attachment) theory, I stopped. I then increased my thyroid, added small doses of aspirin and began large doses of taurine, a precursor to oxytocin. Thyroid, aspirin, and oxytocin are all thermogenic, and within a day I was no longer lonely or craving hot baths. I only wish I had taken various types of peripheral temperature reading throughout the experience to confirm my efforts and intuition. I suppose I could at any point repeat the whole cycle with that in mind, but who wants to feel that lonely. 

Beyond my recent experience, attachment systems seem to stay with us into adulthood which begs a question about how the initial parental warmth or lack of warmth condition becomes embodied in the child-organism. Hans Ijzerman makes the suggestion that “relationship cognition is fundamentally linked to the body’s regulation of temperature”. Within that framework we can move our investigation out of the brain and back into the body. Love and bonding in this view is much less abstract and much more visceral and metabolic. The consistency or inconsistency of a mother’s responses becomes critical to the infant’s attachment style. Consistent warm responses and their actual provision of warmth or succor will provide continuous reinforcement and secure associations, whereas inconsistency will drive anxiety into the association with the primary attachment. Presumably avoidance is simply a strategy to reduce or manage anxiety, while not being physiologically different, just my hunch. Consistent warm touch and milk inform the child that the world is secure and that he or she can use more resources to develop, including development of higher cognitive functioning to aid in greater exploration of the environment which hints and psychological traits like extraversion and openness and their relationship to attachment.

The way I am explaining the evolutionary situation to myself is that an anxious mother is either dispositionally anxious or in an anxiety inducing state from her environment and that will then drive the type of care delivered to her offspring. On the most basic level being anxious is consistent with having less metabolic resources for heat, attention and milk production. Adaptively, it also makes sense for offspring to be more sensitive to threats in an environment the mother is reacting to as threatening. In rat mothers infanticide and canabalism are quite commonly observed in the lab and it is known to result from the mother’s stress. While human mother’s may not usually go quite as far it’s possible that conditions like postpartum depression are a way mothers cut their metabolic losses of parenting in less conducive environments. The concomitant deficits of progesterone and oxytocin are consistent with a reduced metabolism and lowered peripheral heat as well as lowered mood.

The predictive model that our brain uses for thermoregulation and metabolism is radically embodied and is in large part ignorant to the source of its information. This is a very important point: because we are blind to the internal causes of affect, it is extremely common for us to project our inner body’s state change out onto the world. I am more and more convinced that the flavors, textures, and tones of thoughts we experience are highly dependent on the state of the body with small causal arrows flowing from the mind back to the body. The mind seems most successful at changing mood when it simply focuses on managing body basics, like breath rate, sleep, heat, sufficient calories, sufficient protein etc. I know it is a very counterintuitive position as we naturally and deeply identify ourselves with our thoughts.

Our brains work off of rapid non-cognitive associations much more than deliberative evaluations. Studies show that you feel more warm towards someone when you are holding something warm. This happens to be perfectly consistent with the allostatic model of affective realism. A different and clever example of affective realism comes from studies of attraction done comparing attractiveness of a researcher in a neutral setting vs on a high bridge. The autonomic arousal of being well above the ground on a bridge makes the evaluated person seem more attractive because we do not and cannot separately identify the variety of inputs to our arousal or metabolic systems. 

Lisa Barrett Feldman, whom I’ve written about a few times, clarified the importance of metabolism to us and the functioning of our brains: 

“metabolism and other forms of energy regulation may be at the core of the human mind, regardless of whether a person is thinking, feeling or perceiving”

In this view we are creatures preoccupied with energy and heat, and for most of us that concern is usually understood only opaquely and is almost always mediated through many other physical sensations, emotions and cultural concepts. Knowing the central importance of heat and energy and that we are naive to our thermo-metabolic inputs can allow us to better manage ourselves and our relationships outside. Well ahead of me on this, Hans Ijzerman, notes that mild hyperthermia, which is known to improve mood, might be paired with a partner to promote the association with security in a relationship. Sharing the sauna, hot bath or a tropical vacation presently and pleasantly come to mind, but it is likely that consistency also needs to play a role. 

Other physiological options related to temperature include: thyroid, oxytocin, 3,4-Methyl​enedioxy​methamphetamine (MDMA) and increased calories and protein consumption. In terms of diet, perhaps hunter gathers returning successful from a hunt increased calories and protein consumption of their social groups which would drive enhanced bonding. This idea accords reasonably well with our modern conceptions of feasts, festivals, and holidays. Alcohol seems to increase vasodilation and the perception of warmth while actually lowering the core temperature in both the immediate and long term. Oxytocin is critical to maternal-infant pair bonding as well as thermoregulation, but Ijzerman did not mention its potential for external use. The social use of thyroid seems completely unexplored, but the emotional consequences of low thyroid on individuals are well known. Low thyroid is associated with a variety of symptoms: stress, overwhelm, depression, tearfulness, mood swings, ease to anger and even cognitive dysfunction and dementia. Of course and in typical tragic fashion, modern medicine manages thyroid to an ever decreasing group average and then allows “benign hypothyroidism” even beyond that, paying essentially no attention to the psychological, social and long term physical implications. Exogenous oxytocin has been recently re-envisioned by findings from Jaak Panksepp that demonstrate its dramatic effect in reducing separation anxiety essentially by increasing what he describes as confidence. As an interesting reframe, confidence might simply be the same as, or closely related to, an increased metabolism or confidence of energetic resource availability.  

In my experiences with exogenous oxytocin, it does seem to have prosocial effects in a dose dependent manner, but with strongly specific thoughts and feelings towards one person. Might that simply be related to temperature? The singularity of my thoughts was fascinating, and even had me wondering about my sense of attachment.Was more confidence making me feel more securely attached? Oxytocin works on the order of minutes while MDMA works over the course of hours, and while oxytocin may increase peripheral temperature a tenth of a degree MDMA reliably increases the peripheral temperature and does so up-to about 1 degree celsius. Unfortunately, I am yet to feel the difference of MDMA but through existing scientific literature, its therapeutic history and anecdotes from responsible friends clearly highlight MDMA as a potent tool for relationships. Therefore it’s also a tragically regulated substance. In case you might not be aware, MDMA was used for couples counseling before being a party drug and also before being banned. 

Other potential prospects for increased individual or shared peripheral heat include: hot baths, exercise, shared tea and coffee, and shared meals especially with pro-metabolic nutrients and an emphasis on sufficient protein. Protein is the most thermogenic of the macronutrients. Low levels of endorphins are also hyperthermic. Endorphin receptors are supported by oxytocin and endorphins are released in response to both human connection and exercise. Curiously, another “love” drug lysergic diethyl-amide (LSD) is also known to promote hyperthermia, and this begs some good questions about what it does to metabolism and how those might relate to the subjective effects.  Relatedly, floating in deprivation tanks is something I quite enjoy, and while it’s not terribly different in some ways to a warm bath, the water temperature being held at or just above core body temperature is likely a critical part of it’s perceived effect. Personally I suggest turning the temperature up 1 or more degrees celsius, but to do so you need liver or recently ingested glucose to prevent the rise in metabolism from causing a stress response. Sharing as a couple is a good option considering the embodied association, and I would recommend it more heartily if the operators were not generally charging one pod rental for the price of two.

In sum, consider the association of heat in your life and in your relationships. It seems very useful to internalize the way our bodies direct our minds, moods, and associations even if we intuitively think it might make no sense.  At the core of feeling good and sometimes feeling hot is our actual bodily metabolism. I hope you will enjoy some new ideas for feeling and being less lonely and more warm alone or together and if you try anything I've suggested or find any new applications within the same perspective please let me know.

Selected References:

How Emotions Are made

The Archeology of the Mind

Climate, Catastrophe, and Faith

Heartwarming

An active inference theory of allostasis and interoception in depression | Philosophical Transactions of the Royal Society B: Biological Sciences

Modernizing Relationship Therapy through Social Thermoregulation Theory: Evidence, Hypotheses, and Explorations

Toward a radically embodied neuroscience of attachment and relationships

A theory of social thermoregulation in human primates

Your mother, metaphors, and other monkey business: How experiences of physical warmth shape how we think about relationships | In-Mind

Extreme Hyperthermia After LSD Ingestion | JAMA

]]>